Professional Documents
Culture Documents
1
Textbooks
Selected chapters from the following text books
(See course description)
2
What is Cell Biology?
3
What does cell biology explain?
Cell biology explains:
• Cellular structure
• Organization of cellular organelles,
• Cells physiological properties,
• Cellular metabolic processes,
• Cellular signaling pathways
• Cells life cycle
• Interactions with their environment.
• Cytoskeleton, cell adhesion, and
motility
4
Why do we study cell biology?
5
Overview: The Fundamental Units of Life
• All organisms are made of cells
• The cell is the simplest collection of matter
that can be alive
• Cell structure is correlated to cellular function
• All cells are related by their descent from earlier
cells
6
© 2011 Pearson Education, Inc.
Concept 6.2: Eukaryotic cells have internal
membranes that compartmentalize their
functions
• The basic structural and functional unit of every
organism is one of two types of cells: prokaryotic
or eukaryotic
• Only organisms of the domains Bacteria and
Archaea consist of prokaryotic cells
• Protists, fungi, animals, and plants all consist of
eukaryotic cells
7
© 2011 Pearson Education, Inc.
Comparing Prokaryotic and Eukaryotic
Cells
• Basic features of all cells
– Plasma membrane
– Semifluid substance called cytosol
– Chromosomes (carry genes)
– Ribosomes (make proteins)
8
© 2011 Pearson Education, Inc.
9
• Prokaryotic cells are characterized by having
– No nucleus
– DNA in an unbound region called the nucleoid
– No membrane-bound organelles
– Cytoplasm bound by the plasma membrane
10
© 2011 Pearson Education, Inc.
Figure 6.5
Nucleoid
Ribosomes
Plasma
membrane
Bacterial
chromosome Cell wall
Capsule
0.5 m
(a) A typical Flagella (b) A thin section
rod-shaped through the
bacterium bacterium Bacillus
coagulans (TEM)
11
• Eukaryotic cells are characterized by having
– DNA in a nucleus that is bounded by a
membranous nuclear envelope
– Membrane-bound organelles
– Cytoplasm in the region between the plasma
membrane and nucleus
• Eukaryotic cells are generally much larger than
prokaryotic cells
12
© 2011 Pearson Education, Inc.
• The plasma membrane is a selective barrier
that allows sufficient passage of oxygen,
nutrients, and waste to service the volume of
every cell
• The general structure of a biological membrane
is a double layer of phospholipids
13
© 2011 Pearson Education, Inc.
Figure 6.6
(a) Transmission electron micrograph (TEM)
Outside of cell of a plasma membrane
Inside of cell
0.1 m
Carbohydrate side chains
Hydrophilic
region
Hydrophobic
region
Hydrophilic Phospholipid Proteins
region
(b) Structure of the plasma membrane 14
A Panoramic View of the Eukaryotic Cell
• A eukaryotic cell has internal membranes that
partition the cell into organelles
• Plant and animal cells have most of the same
organelles
15
© 2011 Pearson Education, Inc.
Figure 6.8a
Microvilli
Golgi apparatus
Peroxisome
Mitochondrion Lysosome
16
Concept 6.3: The eukaryotic cell’s genetic
instructions are housed in the nucleus and
carried out by the ribosomes
• The nucleus contains most of the DNA in a eukaryotic
cell
• Ribosomes use the information from the DNA to make
proteins
• The nucleus contains most of the cell’s genes
• The nuclear envelope encloses the nucleus, separating
it from the cytoplasm
• The nuclear membrane is a double membrane; each
membrane consists of a lipid bilayer
17
© 2011 Pearson Education, Inc.
Figure 6.9a
Nucleus
Nucleolus
Chromatin
Nuclear envelope:
Inner membrane
Outer membrane
Nuclear pore
Rough ER
Pore
complex
Ribosome
Close-up
of nuclear Chromatin
envelope 18
Ribosomes: Protein Factories
• Ribosomes are particles made of ribosomal
RNA and protein
• Ribosomes carry out protein synthesis in two
locations
– In the cytosol (free ribosomes)
– On the outside of the endoplasmic reticulum or
the nuclear envelope (bound ribosomes)
19
© 2011 Pearson Education, Inc.
Figure 6.10
0.25 m
Small
subunit
TEM showing ER and
ribosomes Diagram of a ribosome
20
Concept 6.4: The endomembrane system
regulates protein traffic and performs
metabolic functions in the cell
• Components of the endomembrane system
– Nuclear envelope
– Endoplasmic reticulum
– Golgi apparatus
– Lysosomes
– Plasma membrane
• These components are either continuous or
connected via transfer by vesicles
21
© 2011 Pearson Education, Inc.
The Endomembrane System: A Review
• The endomembrane system is a complex and
dynamic player in the cell’s compartmental
organization
22
© 2011 Pearson Education, Inc.
Figure 6.15-3
Nucleus
Rough ER
Smooth ER
cis Golgi
Plasma
membrane
trans Golgi
23
The Endoplasmic Reticulum: Biosynthetic
Factory
• The endoplasmic reticulum (ER) accounts for
more than half of the total membrane in many
eukaryotic cells
• The ER membrane is continuous with the
nuclear envelope
• There are two distinct regions of ER
– Smooth ER, which lacks ribosomes
– Rough ER, surface is studded with ribosomes
24
© 2011 Pearson Education, Inc.
Figure 6.11 Smooth ER
Nuclear
envelope
Rough ER
ER lumen
Cisternae Transitional ER
Ribosomes
Transport vesicle
200 nm
Smooth ER Rough ER
25
Functions of ER
• The smooth ER
– Synthesizes lipids
– Metabolizes carbohydrates
– Detoxifies drugs and poisons
– Stores calcium ions
• The rough ER
– Has bound ribosomes, which secrete
glycoproteins (proteins covalently bonded to
carbohydrates)
– Distributes transport vesicles, proteins
surrounded by membranes
– Is a membrane factory for the cell
26
© 2011 Pearson Education, Inc.
The Golgi Apparatus: Shipping and
Receiving Center
• The Golgi apparatus consists of flattened
membranous sacs called cisternae
• Functions of the Golgi apparatus
– Modifies products of the ER
– Manufactures certain macromolecules
– Sorts and packages materials into transport
vesicles
27
© 2011 Pearson Education, Inc.
Figure 6.12
cis face
(“receiving” side of 0.1 m
Golgi apparatus)
Cisternae
trans face
(“shipping” side of TEM of Golgi apparatus
Golgi apparatus)
28
Lysosomes: Digestive Compartments
• A lysosome is a membranous sac of
hydrolytic enzymes that can digest
macromolecules
• Lysosomal enzymes can hydrolyze proteins,
fats, polysaccharides, and nucleic acids
• Lysosomal enzymes work best in the acidic
environment inside the lysosome
29
© 2011 Pearson Education, Inc.
• Some types of cell can engulf another cell by
phagocytosis; this forms a food vacuole
• A lysosome fuses with the food vacuole and
digests the molecules
• Lysosomes also use enzymes to recycle the
cell’s own organelles and macromolecules, a
process called autophagy
30
© 2011 Pearson Education, Inc.
Figure 6.13
1 m Vesicle containing
Nucleus two damaged 1 m
organelles
Mitochondrion
fragment
Lysosome Peroxisome
fragment
Digestive
enzymes
Lysosome
Lysosome
Plasma membrane Peroxisome
Digestion
31
Concept 6.5: Mitochondria
• Mitochondria are the sites of cellular respiration,
a metabolic process that uses oxygen to
generate ATP
10 m
Intermembrane space
Outer Mitochondria
membrane
DNA
Inner
Free Mitochondrial
membrane
ribosomes DNA
in the Cristae
mitochondrial Nuclear DNA
Matrix
matrix
0.1 m
(a) Diagram and TEM of mitochondrion (b) Network of mitochondria in a protist
cell (LM)
32
© 2011 Pearson Education, Inc.
Mitochondria: Chemical Energy Conversion
• Mitochondria are in nearly all eukaryotic cells
• They have a smooth outer membrane and an
inner membrane folded into cristae
• The inner membrane creates two compartments:
intermembrane space and mitochondrial matrix
• Some metabolic steps of cellular respiration are
catalyzed in the mitochondrial matrix
• Cristae present a large surface area for enzymes
that synthesize ATP
33
© 2011 Pearson Education, Inc.
Peroxisomes: Oxidation
• Peroxisomes are specialized metabolic
compartments bounded by a single membrane
• Peroxisomes produce hydrogen peroxide and
convert it to water
• Peroxisomes perform reactions with many
different functions
• How peroxisomes are related to other organelles
is still unknown
34
© 2011 Pearson Education, Inc.
Figure 6.19
1 m
Chloroplast
Peroxisome
Mitochondrion
35
Concept 6.6: The cytoskeleton is a network
of fibers that organizes structures and
activities in the cell
• The cytoskeleton is a network of fibers
extending throughout the cytoplasm
• It organizes the cell’s structures and activities,
anchoring many organelles
• It is composed of three types of molecular
structures
– Microtubules
– Microfilaments
– Intermediate filaments 36
© 2011 Pearson Education, Inc.
Figure 6.20
10 m
37
Roles of the Cytoskeleton:
Support and Motility
• The cytoskeleton helps to support the cell and
maintain its shape
• It interacts with motor proteins to produce
motility
• Inside the cell, vesicles can travel along
“monorails” provided by the cytoskeleton
• Recent evidence suggests that the cytoskeleton
may help regulate biochemical activities
38
© 2011 Pearson Education, Inc.
Centrosomes and Centrioles
• In animal cells, the
centrosome has a
pair of centrioles
which are made of
microtubules
(details later in the
course)
39
© 2011 Pearson Education, Inc.
Cilia and Flagella
• Microtubules control the beating of cilia and
flagella, locomotor appendages of some cells
• Cilia and flagella
differ in their beating
patterns
• Cilia and flagella
share a common
structure (details
later in the course)
40
© 2011 Pearson Education, Inc.
Concept 6.7: Extracellular components and
connections between cells help coordinate
cellular activities
• Most cells synthesize and secrete materials that
are external to the plasma membrane
• These extracellular structures include
– Cell walls of plants
– The extracellular matrix (ECM) of animal cells
– Intercellular junctions
41
© 2011 Pearson Education, Inc.
The Extracellular Matrix (ECM) of Animal
Cells
• Animal cells lack cell walls but are covered by an
elaborate extracellular matrix (ECM)
• The ECM is made up of glycoproteins such as
collagen, proteoglycans, and fibronectin
• ECM proteins bind to receptor proteins in the
plasma membrane called integrins
• Functions of the ECM: support, adhesion,
movement, regulation
42
© 2011 Pearson Education, Inc.
Figure 6.30
43
Cell Junctions
• Neighboring cells in tissues, organs, or organ
systems often adhere, interact, and
communicate through direct physical contact
• Intercellular junctions facilitate this contact
• There are several types of intercellular junctions:
examples:
– Tight junctions
– Desmosomes
– Gap junctions
44
© 2011 Pearson Education, Inc.
Tight Junctions, Desmosomes, and Gap
Junctions in Animal Cells
• At tight junctions, membranes of neighboring
cells are pressed together, preventing leakage of
extracellular fluid
• Desmosomes (anchoring junctions) fasten cells
together into strong sheets
• Gap junctions (communicating junctions) provide
cytoplasmic channels between adjacent cells
45
© 2011 Pearson Education, Inc.
Figure 6.32
TEM
0.5 m
Tight junction
Intermediate
filaments
Desmosome
TEM
1 m
Gap
junction
Ions or small
molecules
Space
TEM
between cells
Extracellular
Plasma membranes matrix
of adjacent cells 0.1 m 46
An Najah national University
Faculty of medicine and health sciences
Cell Biology
2nd semester 2023-2024
Lecture 2: Membrane
Structure and Function
• Short notes from Chapter 7 in Campbell biology
1
Overview: Life at the Edge
• The plasma membrane is the boundary that
separates the living cell from its surroundings
• The plasma membrane exhibits selective
permeability, allowing some substances to
cross it more easily than others
2
© 2011 Pearson Education, Inc.
Concept 7.1: Cellular membranes are fluid
mosaics of lipids and proteins
• Phospholipids are the most abundant lipid in the
plasma membrane
• Phospholipids are amphipathic molecules,
containing hydrophobic and hydrophilic regions
• The fluid mosaic model states that a
membrane is a fluid structure with a “mosaic” of
various proteins embedded in it
3
© 2011 Pearson Education, Inc.
• Membranes have been chemically analyzed and
found to be made of proteins and lipids
4
© 2011 Pearson Education, Inc.
Figure 7.2
WATER
Hydrophilic
head
Hydrophobic
tail
WATER
5
Figure 7.3
Phospholipid
bilayer
6
Figure 7.5
Fibers of extra-
cellular matrix (ECM)
Glyco- Carbohydrate
protein
Glycolipid
EXTRACELLULAR
SIDE OF
MEMBRANE
Cholesterol
Microfilaments Peripheral
of cytoskeleton proteins
Integral
protein
CYTOPLASMIC SIDE
OF MEMBRANE
7
The Fluidity of Membranes
• Phospholipids in the plasma membrane can
move within the bilayer
• Most of the lipids, and some proteins, drift
laterally
• Rarely does a molecule flip-flop transversely
across the membrane
8
© 2011 Pearson Education, Inc.
Figure 7.6
9
• As temperatures cool, membranes switch
from a fluid state to a solid state
• The temperature at which a membrane
solidifies depends on the types of lipids
• Membranes rich in unsaturated fatty acids
are more fluid than those rich in saturated
fatty acids
• Membranes must be fluid to work properly;
they are usually about as fluid as salad oil
10
© 2011 Pearson Education, Inc.
• The steroid cholesterol has different effects on
membrane fluidity at different temperatures
• At warm temperatures (such as 37°C),
cholesterol restrains movement of
phospholipids
• At cool temperatures, it maintains fluidity by
preventing tight packing
11
© 2011 Pearson Education, Inc.
Figure 7.8
Fluid Viscous
Cholesterol 12
Membrane Proteins and Their Functions
• A membrane is a collage of different proteins,
often grouped together, embedded in the fluid
matrix of the lipid bilayer
• Proteins determine most of the membrane’s
specific functions
13
© 2011 Pearson Education, Inc.
• Peripheral proteins are bound to the surface
of the membrane
• Integral proteins penetrate the hydrophobic
core
• Integral proteins that span the membrane are
called transmembrane proteins
• The hydrophobic regions of an integral protein
consist of one or more stretches of nonpolar
amino acids, often coiled into alpha helices
14
© 2011 Pearson Education, Inc.
Figure 7.9
EXTRACELLULAR
SIDE
N-terminus
helix
C-terminus
CYTOPLASMIC
SIDE
15
• Six major functions of membrane proteins
– Transport
– Enzymatic activity
– Signal transduction
– Cell-cell recognition
– Intercellular joining
– Attachment to the cytoskeleton and
extracellular matrix (ECM)
16
© 2011 Pearson Education, Inc.
Figure 7.10
Signaling molecule
Receptor
Enzymes
ATP
Signal transduction
(a) Transport (b) Enzymatic activity (c) Signal transduction
Glyco-
protein
18
© 2011 Pearson Education, Inc.
The Permeability of the Lipid Bilayer
• Hydrophobic (nonpolar) molecules, such as
hydrocarbons, can dissolve in the lipid bilayer
and pass through the membrane rapidly
19
© 2011 Pearson Education, Inc.
Transport Proteins
• Transport proteins allow passage of
hydrophilic substances across the membrane
• Some transport proteins, called channel
proteins, have a hydrophilic channel that
certain molecules or ions can use as a tunnel
• Channel proteins called aquaporins facilitate
the passage of water
20
© 2011 Pearson Education, Inc.
• Other transport proteins, called carrier proteins,
bind to molecules and change shape to shuttle
them across the membrane
• A transport protein is specific for the substance
it moves
21
© 2011 Pearson Education, Inc.
Concept 7.3: Passive transport is diffusion of
a substance across a membrane with no
energy investment
• Diffusion is the tendency for molecules to spread
out evenly into the available space
• Although each molecule moves randomly, diffusion
of a population of molecules may be directional
• At dynamic equilibrium, as many molecules cross
the membrane in one direction as in the other
22
© 2011 Pearson Education, Inc.
Figure 7.13
Molecules of dye
Membrane (cross section)
WATER
24
© 2011 Pearson Education, Inc.
Effects of Osmosis on Water Balance
• Osmosis is the diffusion of water across a
selectively permeable membrane
• Water diffuses across a membrane from the
region of lower solute concentration to the
region of higher solute concentration until the
solute concentration is equal on both sides
25
© 2011 Pearson Education, Inc.
Figure 7.14
Lower Higher Same concentration
concentration concentration of solute
of solute (sugar) of solute
Sugar
molecule
H2O
Selectively
permeable
membrane
Osmosis 26
Water Balance of Cells Without Walls
• Tonicity is the ability of a surrounding solution
to cause a cell to gain or lose water
• Isotonic solution: Solute concentration is the
same as that inside the cell; no net water
movement across the plasma membrane
• Hypertonic solution: Solute concentration is
greater than that inside the cell; cell loses
water.
• Hypotonic solution: Solute concentration is
less than that inside the cell; cell gains water
27
© 2011 Pearson Education, Inc.
Figure 7.15
28
• Hypertonic or hypotonic environments create
osmotic problems for organisms
• Osmoregulation, the control of solute
concentrations and water balance, is a necessary
adaptation for life in such environments
29
© 2011 Pearson Education, Inc.
Facilitated Diffusion: Passive Transport
Aided by Proteins
• In facilitated diffusion, transport proteins speed
the passive movement of molecules across the
plasma membrane
• Channel proteins provide corridors that allow a
specific molecule or ion to cross the membrane
• Channel proteins include
– Aquaporins, for facilitated diffusion of water
– Ion channels that open or close in response
to a stimulus (gated channels)
30
© 2011 Pearson Education, Inc.
Figure 7.17
EXTRACELLULAR
FLUID
(a) A channel
protein
Channel protein
Solute
CYTOPLASM
32
© 2011 Pearson Education, Inc.
Concept 7.4: Active transport uses energy to
move solutes against their gradients
• Facilitated diffusion is still passive because the
solute moves down its concentration gradient,
and the transport requires no energy
• Some transport proteins, however, can move
solutes against their concentration gradients
33
© 2011 Pearson Education, Inc.
The Need for Energy in Active Transport
• Active transport moves substances against
their concentration gradients
• Active transport requires energy, usually in the
form of ATP
• Active transport is performed by specific
proteins embedded in the membranes
• Active transport allows cells to maintain
concentration gradients that differ from their
surroundings
• The sodium-potassium pump is one type of
active transport system 34
© 2011 Pearson Education, Inc.
Figure 7.18-6
Na+ Na+
Na+
K+
K+
K+
K+
K+
P
6 K+ 5 4 Pi
35
Figure 7.19
Passive transport Active transport
36
Cotransport: Coupled Transport by a
Membrane Protein
• Cotransport occurs when active transport of a
solute indirectly drives transport of other
solutes
• Symport
• Antiport
37
© 2011 Pearson Education, Inc.
Concept 7.5: Bulk transport across the
plasma membrane occurs by exocytosis
and endocytosis
• Small molecules and water enter or leave the
cell through the lipid bilayer or via transport
proteins
• Large molecules, such as polysaccharides and
proteins, cross the membrane in bulk via
vesicles
• Bulk transport requires energy
38
© 2011 Pearson Education, Inc.
Exocytosis
• In exocytosis, transport vesicles migrate to the
membrane, fuse with it, and release their
contents
• Many secretory cells use exocytosis to export
their products
39
© 2011 Pearson Education, Inc.
Endocytosis
• In endocytosis, the cell takes in macromolecules
by forming vesicles from the plasma membrane
• Endocytosis is a reversal of exocytosis, involving
different proteins
• There are three types of endocytosis
– Phagocytosis (“cellular eating”)
– Pinocytosis (“cellular drinking”)
– Receptor-mediated endocytosis
40
© 2011 Pearson Education, Inc.
Figure 7.22a
Phagocytosis EXTRACELLULAR
FLUID Solutes
Pseudopodium Pseudopodium
of amoeba
Bacterium
1 m
Food vacuole
Pinocytosis
0.5 m
Plasma
membrane
• In pinocytosis,
molecules are taken up
when extracellular fluid
is “gulped” into tiny
vesicles Vesicle
42
• In receptor-mediated endocytosis, binding of
ligands to receptors triggers vesicle formation
• A ligand is any molecule that binds specifically
to a receptor site of another molecule
43
© 2011 Pearson Education, Inc.
Figure 7.22c
Receptor-Mediated Endocytosis
Plasma Receptor
Coat
membrane proteins Ligand
Coat proteins
Coated
0.25 m
pit
Coated
vesicle
Top: A coated pit. Bottom: A
coated vesicle forming during
receptor-mediated endocytosis
(TEMs).
44
Cell Biology
Course No.: 7104102
2 CH.
1
2
Overview: Cellular Messaging
3
© 2011 Pearson Education, Inc.
Overview: Cellular Messaging
• Unicellular organisms
– can perceive changes in nutrient availability and
adapt their metabolism as needed.
– may utilize environmental signals to locate a
suitable mate;
• The cells of multicellular organisms must
communicate with one another to coordinate
the activities of the organism as a whole.
4
© 2011 Pearson Education, Inc.
Overview: Cellular Messaging
• Biologists have discovered some universal
mechanisms of cellular regulation
• Cells most often communicate with each other
via chemical signals
• For example, the fight-or-flight response is
triggered by a signaling molecule called
epinephrine
5
© 2011 Pearson Education, Inc.
Signaling
• Local • Long-Distance
• Direct contact • hormones
• Cell junctions
• Cell-cell recognition
• Local regulators
• Paracrine signaling
• Synaptic signaling
6
© 2011 Pearson Education, Inc.
Mechanisms of Local Signaling
1. Local signaling by direct contact: two types:
10
11
The Three Stages of Cell Signaling:
A Preview
• Earl W. Sutherland discovered how the
hormone epinephrine acts on cells
• Sutherland suggested that cells receiving
signals went through three processes
– Reception
– Transduction
– Response
12
© 2011 Pearson Education, Inc.
13
Concept 11.2: Reception: A signaling molecule
binds to a receptor protein, causing it to change
shape
• The ability of a cell to respond to a signal depends
on whether or not it has a receptor specific to that
signal
• The binding between a signal molecule (ligand)
and receptor is highly specific
• A shape change in a receptor is often the initial
transduction of the signal
• Most signal receptors are plasma membrane
proteins but others are located inside the cell
14
© 2011 Pearson Education, Inc.
Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind
to specific sites on receptor proteins that
span the plasma membrane
• There are three main types of membrane
receptors
– G protein-coupled receptors
– Receptor tyrosine kinases
– Ion channel receptors
15
© 2011 Pearson Education, Inc.
G-protein-coupled receptor (GPCRs)
• the largest family of cell-surface receptors
• Many different signaling molecules use
GPCRs including:
– yeast mating factors,
– epinephrine (adrenaline), Glucagon and many
other hormones,
– Neurotransmitters: for example serotonin on
serotonin receptors (5HTRs)
16
© 2011 Pearson Education, Inc.
Signaling molecule binding site • A GPCR is a plasma
membrane receptor that
works with the help of a
G protein
G protein-coupled Plasma
receptor membrane
Segment that
interacts with
G proteins GDP
CYTOPLASM
G protein Enzyme
G protein-coupled receptor
(inactive)
18
© 2011 Pearson Education, Inc.
• G protein hydrolysis GTP to GDP rapidly
(has an inherent “intrinsic” GTPase activity)
• This causes:
– inactivation of the G protein,
– its dissociation from the enzyme,
– thus the actions of the G protein–GTP
complex are short-lived
19
© 2011 Pearson Education, Inc.
20
• Malfunctions of the associated G proteins
themselves are involved in many human
diseases, including bacterial infections.
– The bacteria that cause cholera, pertussis
(whooping cough), and botulism, among
others cause illness by producing toxins that
interfere with G protein function.
Activated relay
proteins
Cellular
P Tyr P Tyr Tyr P
Tyr Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P P Tyr Tyr P
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP
response 2
Activated tyrosine Fully activated
kinase regions receptor tyrosine
(unphosphorylated kinase Inactive
dimer) (phosphorylated relay proteins
3 4
dimer) 23
Cancer and RTKs:
• Abnormal functioning of RTKs is associated with many types
of cancers.
– Example: breast cancer patients have a poor prognosis if
their tumor cells harbor excessive levels of an RTK called
HER2.
• Using molecular biological techniques, researchers have
developed a protein (monoclonal antibody) called
Trastuzumab (Herceptin®) that binds to HER2
receptors on cells, prevent their dimerization and inhibits
cell division, thus preventing further tumor development.
24
© 2011 Pearson Education, Inc.
Ligand-gated ion channel
• a membrane receptor containing a region that
acts as a gate when the receptor changes shape
• When a signal molecule binds as a ligand to
the receptor, the gate allows specific ions, such
as Na+ or Ca2+, to pass through the channel in
the receptor
Gate
closed Ions Gate Gate closed
Signaling open
molecule
(ligand)
Cellular
response
26
© 2011 Pearson Education, Inc.
Ligand-gated
Acetyl choline gated-
ion channels
Monovalent cation channel are very
important in
the nervous
system.
27
© 2011 Pearson Education, Inc.
Receptors in the Plasma Membrane:
cell surface receptors
• cell-surface receptors represent 30% of all
human proteins but determining their structures
has proved challenging:
– only 1% of cell-surface receptors structures have
been determined
28
© 2011 Pearson Education, Inc.
Intracellular Receptors
• Intracellular receptor proteins are found in the
cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers
can readily cross the membrane and activate
receptors
• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals and
Nitric Oxide gas
29
© 2011 Pearson Education, Inc.
How the intracellular Receptors work?
1. The hormone has entered a cell,
2. Binds to the intracellular receptor in the
cytoplasm or the nucleus.
3. The binding changes the receptor into a
hormone-receptor complex that is able to cause
a response
– in many cases, the turning on or off of
particular genes.
30
© 2011 Pearson Education, Inc.
Example: Aldosterone
1. secreted by cells of the adrenal gland
2. Aldosterone then travels through the blood
and enters cells all over the body. (response
occurs mainly in kidney cells)
3. In these cells, the hormone binds to the
receptor protein, activating it.
4. the active form of the receptor protein then
enters the nucleus and turns on specific
genes
31
© 2011 Pearson Education, Inc.
Example: Aldosterone (cont.)
5. The genes control water and sodium flow in
kidney cells, ultimately affecting blood
volume
• When the aldosterone receptor is
activated, it acts as a transcription
factor that turns on specific genes.
33
Concept 11.3: Transduction: Cascades
of molecular interactions relay signals
from receptors to target molecules in
the cell
• Signal transduction pathway usually involves
multiple steps (plasma membrane receptors)
• Multistep pathways can amplify a signal: A few
molecules can produce a large cellular response
• Multistep pathways provide more opportunities
for coordination and regulation of the cellular
response
34
© 2011 Pearson Education, Inc.
Signal Transduction Pathways
• The molecules that relay a signal from receptor
to response are mostly proteins
• Like falling dominoes, the receptor activates
another protein, which activates another, and so
on, until the protein producing the response is
activated
• At each step, the signal is transduced into a
different form, usually a shape change in a
protein (Very often, shape change is brought
about by phosphorylation) 35
© 2011 Pearson Education, Inc.
Protein Phosphorylation and
Dephosphorylation
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylations
• Protein kinases transfer phosphates from ATP
to protein, a process called phosphorylation
Protein kinase
(enzyme)
Protein Protein-P
(Substrate-1) (Product-2)
ATP ADP
(Substrate-2) (Product-2) 36
© 2011 Pearson Education, Inc.
• Protein phosphatases remove the phosphates
from proteins, a process called dephosphorylation
Protein
Phosphatase
Protein-P (enzyme) Protein
(Substrate) (Product-1)
PO43-
(Product-2)
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1 Active
protein
kinase
1
Inactive
protein kinase ATP
2 ADP P
Active
protein
PP kinase
Pi 2
Inactive
protein kinase ATP
3 ADP P
Active
protein
PP kinase
Pi 3
Inactive
protein ATP
ADP P
Active Cellular
PP
protein response
Pi 38
Small Molecules and Ions as Second
Messengers
• The extracellular signal molecule (ligand)
that binds to the receptor is a pathway’s
“first messenger”
• Second messengers are small, nonprotein,
water-soluble molecules or ions that spread
throughout a cell by diffusion
39
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Small Molecules and Ions as Second
Messengers
• Second messengers participate in pathways
initiated by GPCRs and RTKs
• Cyclic AMP and calcium ions are common
second messengers
40
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Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely
used second messengers
41
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Figure 11.11
42
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Figure 11.11a
43
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Figure 11.11b
44
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• Many signal molecules trigger formation of
cAMP
• Other components of cAMP pathways are G
proteins, G protein-coupled receptors, and
protein kinases
• cAMP usually activates protein kinase A, which
phosphorylates various other proteins
• Further regulation of cell metabolism is provided
by G-protein systems that inhibit adenylyl
cyclase
45
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First messenger
(signaling molecule
such as epinephrine)
Adenylyl
G protein cyclase
G protein-coupled GTP
receptor
ATP
Second
cAMP messenger
Protein
kinase A
Cellular responses
46
The ability of a hormone or neurotransmitter to stimulate or
inhibit AC depends on the type of G protein that is linked to
the receptor.
• One type, designated Gs, stimulates AC,
• whereas another type, designated Gi, inhibits the enzyme 47
Cholera toxin
• an enzyme that chemically modifies a G protein
involved in regulating salt and water secretion.
– Because the modified G protein is unable to
hydrolyze GTP to GDP, it remains stuck in its
active form, continuously stimulating adenylyl
cyclase to make cAMP.
Viagra (sildenafil)
• A compound that inhibits the hydrolysis of
cGMP to GMP (Phosphodiesterase inhibitor)
– a treatment for erectile dysfunction in human males.
48
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Calcium Ions and Inositol Triphosphate
(IP3)
• Calcium ions (Ca2+) act as a second messenger
in many pathways
• Calcium is an important second messenger
because cells can regulate its concentration
49
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EXTRACELLULAR Plasma
FLUID membrane
Ca2+
ATP pump
Mitochondrion
Ca2+
concentration in
the cytosol is Nucleus
usually much
lower than in
CYTOSOL
the extracellular
fluid and ER
Ca2+
pump
Endoplasmic
Ca2+ reticulum
ATP pump (ER)
51
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Figure 11.14-1
EXTRA-
Signaling molecule Example: 1-adrenergic
CELLULAR
FLUID (first messenger) receptor in liver cells
G protein
DAG
GTP
G protein-coupled PIP2
Phospholipase C
receptor
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic Ca2+
reticulum (ER)
CYTOSOL 52
Figure 11.14-2
EXTRA-
Signaling molecule Example: 1-adrenergic
CELLULAR
FLUID (first messenger) receptor in liver cells
G protein
DAG
GTP
G protein-coupled PIP2
Phospholipase C
receptor
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic Ca2+
reticulum (ER)
Ca2+
(second
CYTOSOL messenger) 53
Figure 11.14-3
EXTRA-
Signaling molecule Example: 1-adrenergic
CELLULAR
FLUID (first messenger) receptor in liver cells
G protein
DAG
GTP
G protein-coupled PIP2
Phospholipase C
receptor
IP3
(second messenger)
IP3-gated
calcium channel
Various Cellular
Endoplasmic Ca2+ proteins
reticulum (ER) responses
activated
Ca2+
(second
CYTOSOL messenger) 54
Concept 11.4: Response: Cell signaling
leads to regulation of transcription or
cytoplasmic activities
55
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Nuclear and Cytoplasmic Responses
• Ultimately, a signal transduction pathway leads
to regulation of one or more cellular activities
• The response may occur in the cytoplasm or in
the nucleus
• Many signaling pathways regulate the
synthesis of enzymes or other proteins,
usually by turning genes on or off in the
nucleus
• The final activated molecule in the signaling
pathway may function as a transcription factor
56
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Growth factor
Nuclear responses to a Reception
Receptor
signal: the activation
of a specific gene by a
growth factor Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive Active
transcription transcription
factor factor Response
P
DNA
Gene
NUCLEUS mRNA 57
• Sometimes signaling pathways regulate the
activity of enzymes rather than their synthesis
– Epinephrine signal on liver cells for example
ultimately leads to glycogen degradation by the
activation of glycogen phosphorylase enzyme
• Other signals may cause the opening or closing
of an ion channel in the plasma membrane or a
change in cell metabolism
• Signaling pathways can also affect the overall
behavior of a cell, for example, changes in cell
shape
58
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First messenger
(signaling molecule
such as epinephrine)
Adenylyl
G protein cyclase
G protein-coupled GTP
receptor
ATP
Second
cAMP messenger
Protein
kinase A
60
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Signal Amplification
• Enzyme cascades amplify the cell’s response
• At each step, the number of activated products is
much greater than in the preceding step
61
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62
The Specificity of Cell Signaling and
Coordination of the Response
• Different kinds of cells have different collections
of proteins (different sets of genes are on)
• These different proteins allow cells to detect and
respond to different signals
• Even the same signal can have different effects in
cells with different proteins and pathways
• Pathway branching and “cross-talk” further help
the cell coordinate incoming signals
63
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The Specificity of Cell Signaling and
Coordination of the Response
Signaling
molecule
Receptor
Relay
Activation
molecules
or inhibition
Cell A. Pathway leads Cell B. Pathway branches, Cell C. Cross-talk occurs Cell D. Different receptor
to a single response. leading to two responses. between two pathways. leads to a different
response.
64
Signaling
molecule
Receptor
Relay
molecules
Response 4 Response 5
67
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Signaling Plasma
molecule membrane
Receptor
Three
different
protein
kinases
Scaffolding
protein
One scaffolding protein isolated from mouse brain cells holds three
protein kinases and carries these kinases with it when it binds to an
appropriately activated membrane receptor; it thus facilitates a specific
68
phosphorylation cascade (The above Figure).
Wiskott-Aldrich syndrome (WAS)
• a primary human immunodeficiency
• X-linked recessive inherited disorder
• absence of a single relay protein (WASp) leads to
diverse effects
• abnormal bleeding (due to thrombocytopenia),
eczema, a predisposition to infections,
autoimmunity and leukemia.
• symptoms are thought to arise primarily from
the absence of the protein in cells of the
immune system.
69
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Wiskott-Aldrich syndrome (WAS)
• WAS protein is located just beneath the immune
cell surface and interacts both with:
• microfilaments of the cytoskeleton
• and with several different components of
signaling pathways that relay information
from the cell surface, including pathways
regulating immune cell proliferation.
• When the WAS protein is absent, the
cytoskeleton is not properly organized and
signaling pathways are disrupted, leading to the
WAS symptoms. 70
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Termination of the Signal
• Inactivation mechanisms are an essential
aspect of cell signaling
• It prepares the cell to respond to a fresh signal.
• Abnormal signaling often seen in tumor cells is
proof that the termination of a signal at the
appropriate time can be just as important as the
initiation of a signal.
• Remember the cholera toxin and G protein
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Receptor inactivation :
1. If ligand concentration falls, fewer receptors
will be bound (the binding of the ligand to the
receptor is reversible)
2. Unbound receptors revert to an inactive state
3. The cellular response occurs only when the
concentration of receptors with bound signaling
molecules is above a certain threshold. When
the number of active receptors falls below that
threshold, the cellular response ceases.
72
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Termination of the Signal
Relay molecules inactivation: differs
according to the molecule
• The GTPase activity intrinsic to a G protein
hydrolyzes its bound GTP
• the enzyme phosphodiesterase converts
cAMP to AMP;
• protein phosphatases inactivate
phosphorylated kinases and other proteins;
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Concept 11.5: Apoptosis integrates
multiple cell-signaling pathways
• Apoptosis is programmed or controlled cell
suicide
– from Greek apoptōsis ‘falling off’, from apo
‘from’ + ptōsis ‘falling, a fall’.
• Cells that are infected, damaged, or have
reached the end of their functional life span
often undergo “programmed cell death”
74
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Concept 11.5: Apoptosis integrates
multiple cell-signaling pathways
• Components of the cell are chopped up and
packaged into vesicles that are digested by
scavenger cells
75
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Figure 11.20
2 m
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Example: Apoptosis in the Soil Worm
Caenorhabditis elegans
• Etymology: 'Caeno' and 'rhabditis' derived from
Greek, means 'recent' and 'rod-like' respectively.
• 'Elegans' is derived from Latin, means 'elegant'
due to the elegant sinusoidal movement of this
nematode (WIKIBOOKS)
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Apoptosis in the Soil Worm Caenorhabditis
elegans
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Apoptosis in the Soil Worm Caenorhabditis
elegans
When there is no death signal:
• As long as Ced-9, located in the outer
mitochondrial membrane, is active, apoptosis is
inhibited, and the cell remains alive.
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Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Ced-4 Ced-3
Receptor
for death- Inactive proteins
signaling
molecule
(a) No death signal 82
When a cell receives a death signal:
83
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Ced-9 Cell
(inactive) forms
blebs
Death-
signaling
molecule
Activation Nucleases
cascade
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• Apoptosis is essential for the development
and maintenance of all animals
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Syndactyly
87
• Apoptosis may be involved in some diseases
(for example, Parkinson’s and Alzheimer’s);
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• Interference with apoptosis may contribute
to some cancers
– cancer can result from a failure of cell
suicide; some cases of human melanoma,
for example, have been linked to faulty
forms of the human version of the C.
elegans Ced-4 protein.
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Cell Biology
Course No.: 7104102
2 CH.
1
© 2011 Pearson Education, Inc. 2
The Body’s Long-Distance Regulators
• Hormones serve as messengers, controlling
and coordinating activities throughout the
body.
3
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Two systems coordinate communication
throughout the body: the endocrine system and
the nervous system
– The endocrine system secretes hormones (chemical
signals) that coordinate slower but longer-acting
responses including reproduction, development,
energy metabolism, growth, and behavior
– The nervous system conveys high-speed electrical
signals along specialized cells called neurons; these
signals in turn regulate neurons, muscle cells, and
endocrine cells
– The two systems often overlap in function.
4
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Concept 45.1: Hormones and other
signaling molecules bind to target receptors,
triggering specific response pathways
Intercellular Communication
• The ways that signal are transmitted
between animal cells are classified by
two criteria
– The type of secreting cell
– The route taken by the signal in
reaching its target
5
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Endocrine Signaling
• Hormones secreted into extracellular fluids by
endocrine cells reach their targets via the
bloodstream (or heamolymph)
Blood
vessel Response
7
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Paracrine and Autocrine Signaling
• Local regulators are molecules that act over
short distances, reaching target cells solely by
diffusion After secretion, they act on their
target cells within seconds or even
milliseconds.
– In paracrine signaling, the target cells lie near
the secreting cells
– In autocrine signaling, the target cell is also the
secreting cell
8
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Response
Response
11
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Synaptic and Neuroendocrine Signaling
• In synaptic signaling, neurons form
specialized junctions with target cells (neurons,
muscles, or glands) called synapses
– At synapses, neurons secrete molecules
called neurotransmitters that diffuse very
short distances and bind to receptors on
target cells
• Neurotransmitters are central to sensation,
memory, cognition, and movement
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Synaptic and Neuroendocrine Signaling
• In neuroendocrine signaling, specialized
neurons called neurosecretory cells secrete
neurohormones, which diffuse from nerve cell
endings into the bloodstream.
– Antidiuretic hormone example of a
neurohormone is, which is essential to kidney
function and water balance.
– Many neurohormones function in the regulation
of endocrine signaling
13
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Synapse
Neuron
Response
Neurosecretory
cell
Blood Response
vessel
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Nitric oxide (NO)
• A gas functions as both a local regulator and
a neurotransmitter.
• Synthesized and released from endothelial
cells in blood vessel walls when the level of
oxygen in the blood falls,
• diffuses into the surrounding smooth muscle
cells then activates an enzyme that relaxes
the cells.
• The result is vasodilation, which increases
blood flow to tissues
16
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Nitric oxide (NO)
• In human males, NO’s ability to promote
vasodilation enables sexual function by
increasing blood flow into the penis,
producing an erection.
– The drug Viagra (sildenafil citrate), a
treatment for male erectile dysfunction,
sustains an erection by prolonging activity of
the NO response pathway.
17
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18
Chemical Classes of Local Regulators
and Hormones
Classes of Hormones
• Three major classes of molecules function as
hormones in vertebrates
– Polypeptides (proteins and peptides)
– Amines derived from amino acids
– Steroid hormones
19
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Figure 45.5
Water-soluble (hydrophilic) Lipid-soluble (hydrophobic)
Polypeptides Steroids
0.8 nm
Insulin Cortisol
Amines
Epinephrine Thyroxine 20
• hormones vary in their solubility in aqueous
and lipid-rich environments.
– Polypeptides and most amine hormones are
water-soluble,
– whereas steroid hormones and other largely
nonpolar (hydrophobic) hormones, such as
thyroxine, are lipid-soluble.
21
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Cellular Response Pathways
• Water and lipid soluble hormones differ in
their paths through a body
• Water-soluble hormones are secreted by
exocytosis, travel freely in the bloodstream,
and bind to cell-surface receptors
• Lipid-soluble hormones diffuse across cell
membranes, travel in the bloodstream bound
to transport proteins, and diffuse through the
membrane of target cells
22
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• Lipid-soluble hormones (steroid and thyroid
hormones) pass easily through cell membranes,
while water-soluble hormones (polypeptides
and amines) do not
• The solubility of a hormone correlates with the
location of receptors inside or on the surface of
target cells
23
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Figure 45.6-2
SECRETORY
CELL
Water- Lipid-
soluble soluble
hormone hormone
VIA
BLOOD
Transport
Signal receptor protein
TARGET OR
CELL Signal
receptor
Cytoplasmic
response Gene
regulation
Cytoplasmic
response Gene
regulation
NUCLEUS
(a) (b) 24
Pathway for Water-Soluble Hormones
• Binding of a hormone to its receptor initiates a
signal transduction pathway leading to
responses in the cytoplasm, enzyme
activation, or a change in gene expression
25
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• The hormone epinephrine has multiple
effects in mediating the body’s response to
short-term stress
• Epinephrine binds to receptors on the plasma
membrane of liver cells
• This triggers the release of messenger
molecules that activate enzymes and result in
the release of glucose into the bloodstream
26
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Figure 45.7-2
Epinephrine
Adenylyl
G protein cyclase
G protein-coupled GTP
receptor
ATP
cAMP Second
messenger
Inhibition of Protein
glycogen synthesis kinase A
Promotion of
glycogen breakdown
27
Pathway for Lipid-Soluble Hormones
• The response to a lipid-soluble hormone is
usually a change in gene expression
• Steroids, thyroid hormones, and the hormonal
form of vitamin D enter target cells and bind to
protein receptors in the cytoplasm or nucleus
• Protein-receptor complexes then act as
transcription factors in the nucleus, regulating
transcription of specific genes
28
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Steroid Hormone EXTRACELLULAR
FLUID
Steroid
hormone
receptor Plasma
membrane
Hormone-receptor
complex
NUCLEUS
CYTOPLASM
DNA
New protein
mRNA
29
Multiple Effects of Hormones
30
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Endocrine Tissues and Organs
• In some tissues, endocrine cells are grouped together in
ductless organs called endocrine glands
• Endocrine glands secrete hormones directly into
surrounding fluid
• These contrast with exocrine glands, which have ducts
and which secrete substances onto body surfaces or
into cavities
32
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Major endocrine glands:
تحت المهادHypothalamus
الصنوبريةPineal gland
النخاميةPituitary gland Organs containing
endocrine cells:
الدرقيةThyroid gland
Thymus الزعترية
جارات الدرقيةParathyroid glands
(behind thyroid) Heart
Liver
الفوق كلوية، الكظريةAdrenal glands
(atop kidneys) Stomach
البنكرياسPancreas Kidneys
Small
المبايضOvaries (female) intestine
الخصيتينTestes (male)
33
34
35
Concept 45.2: Feedback regulation and
coordination with the nervous system are
common in endocrine signaling
Simple Hormone Pathways
• Hormones are released from an endocrine cell,
travel through the bloodstream, and interact
with specific receptors within a target cell to
cause a physiological response
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• For example, the
release of acidic
contents of the
stomach into the
duodenum stimulates
endocrine cells there
to secrete secretin
• This causes target
cells in the pancreas,
a gland behind the
stomach, to raise the
pH in the duodenum
37
• In a simple
neuroendocrine
pathway, the stimulus
is received by a
sensory neuron, which
stimulates a
neurosecretory cell
• The neurosecretory
cell secretes a
neurohormone, which
enters the bloodstream
and travels to target
cells
38
Feedback Regulation
• A negative feedback loop inhibits a response
by reducing the initial stimulus, thus preventing
excessive pathway activity
• For instance, bicarbonate release in response to
secretin increases pH in the intestine,
eliminating the stimulus and thereby shutting
off secretin release
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Feedback Regulation
• Positive feedback reinforces a stimulus to
produce an even greater response
• For example, in mammals oxytocin causes the
release of milk, causing greater suckling by
offspring, which stimulates the release of more
oxytocin
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Insulin and Glucagon: Control of Blood
Glucose
• Insulin (decreases blood glucose) and
glucagon (increases blood glucose) are
antagonistic hormones that help maintain
glucose homeostasis
• The pancreas has clusters of endocrine cells
called pancreatic islets with alpha cells that
produce glucagon and beta cells that produce
insulin
41
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Body cells Insulin
take up more Beta cells of
glucose. pancreas
release insulin
into the blood.
Liver takes
up glucose
and stores it STIMULUS:
as glycogen. Blood glucose level rises
Blood glucose
level declines. (for instance, after eating a
carbohydrate-rich meal).
Homeostasis:
Blood glucose level
(70–110 mg/m100mL)
STIMULUS:
Blood glucose Blood glucose level
level rises. falls (for instance, after
skipping a meal).
Liver breaks
down glycogen Alpha cells of pancreas
and releases release glucagon into
glucose into the blood.
the blood. Glucagon 42
Coordination of Endocrine and Nervous
Systems in vertebrates
• In vertebrates, coordination of endocrine
signaling relies heavily on a region of the
brain called the hypothalamus
44
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Figure 45.14
Cerebrum
Pineal
gland Thalamus
Hypothalamus
Cerebellum
Pituitary
Spinal cord gland
Hypothalamus
Posterior
pituitary
Anterior
pituitary
45
Posterior Pituitary Hormones :
هرمونات الغدة النخامية الخلفية
• The posterior pituitary is an extension of the
hypothalamus. Hypothalamic axons that reach
into the posterior pituitary secrete
neurohormones synthesized in the
hypothalamus.
• Certain neurosecretory cells in the
hypothalamus make antidiuretic hormone
(ADH) and oxytocin, which are transported to
the posterior pituitary, where they are stored.
46
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Posterior Pituitary Hormones :
هرمونات الغدة النخامية الخلفية
47
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Figure 45.15
Hypothalamus
Neurosecretory
cells of the
hypothalamus
Neurohormone Axons
Posterior
pituitary
Anterior
pituitary
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Posterior Pituitary Hormones
• In female mammals oxytocin controls
milk secretion by the mammary
glands and regulates uterine
contractions during birthing.
• In addition, oxytocin has targets in the
brain, where it influences behaviors
related to maternal care, pair bonding,
and sexual activity.
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Anterior Pituitary Hormones
هرمونات الغدة النخامية األمامية
• The anterior pituitary is an endocrine
gland that synthesizes and secretes
hormones in response to hormones from the
hypothalamus.
– Hormones secreted by the hypothalamus
control the release of all anterior pituitary
hormones
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• Each hypothalamic hormone is either a
releasing hormone (مطلق، (هرمون محررor an
inhibiting hormone ) (هرمون مثبط, promoting
or inhibiting release of one or more specific
hormones by the anterior pituitary
• For example, prolactin-releasing hormone is a
hypothalamic hormone that stimulates the
anterior pituitary to secrete prolactin (PRL),
which has a role in milk production
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• The hypothalamic releasing and inhibiting
hormones are secreted near capillaries at the
base of the hypothalamus.
• The capillaries drain into short blood
vessels, called portal vessels, which
subdivide into a second capillary bed within
the anterior pituitary.
• Releasing and inhibiting hormones thus have
direct access to the gland they control.
53
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54
Anterior Pituitary Hormones
• hormones from the -
Hypothalamus
hypothalamus, the
anterior pituitary, + Releasing hormone
Negative Feedback
and a target -
Anterior pituitary
endocrine gland are
often organized into + Pituitary hormone
a hormone cascade
pathway which Target Gland
typically involve
negative feedback Target gland hormone
regulation 55
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Anterior Pituitary Hormones
• Hormone cascade pathways redirect signals
from the hypothalamus to other endocrine
glands. For this reason, the anterior pituitary
hormones in these pathways are called tropic
hormones or tropins, from the Greek word for
“bending or turning”.
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Tropic and Nontropic Hormones
• A tropic hormone regulates the function of
endocrine cells or glands, examples: FSH,
LH,TSH, and ACTH
• A non-tropic hormone acts directly on
targeted tissues or cells, and not on other
endocrine cells or glands (usually the last
hormone in the pathway), examples:
Prolactin and MSH
• Some hormones have both effects: example:
GH
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Thyroid Regulation: A Hormone Cascade
Pathway
• Thyroid hormone refers to a pair of hormones
– Triiodothyronine (T3), with three iodine atoms
– Thyroxine (T4) with four iodine atoms
• Released by the thyroid gland
• thyroid hormone regulates
– bioenergetics; helps maintain normal blood
pressure, heart rate, and regulates digestive and
reproductive functions.
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Thyroid Regulation: A Hormone Cascade
Pathway
• If the level of thyroid hormone in the blood
drops, the hypothalamus responds by
initiating a hormone cascade pathway
involving the hypothalamus, anterior
pituitary, and thyroid gland
59
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60
.1انخفاض مستويات
هرمون الدرقية تحت
المدى الطبيعي
«.3الهرمون المحرر
للهرمون المنشط للغدة
الدرقية» يحفز الغدة
النخامية الفراز
«الهرمون المنشط للغدة
الدرقية»
61
«.4الهرمون المنشط
للغدة الدرقية» يحفز
الغدة الدرقية إلفراز
هرمون الدرقية
T3 and T4
.5تعود مستويات
هرمون الدرقية في الدم
والجسم الى مداها
.6هرمون الدرقية يحبط الطبيعي .يعمل هرمون
افراز الهرمون المحرر الدرقية على الخاليا
للهرمون المنبه للغدة الهدف في انحاء الجسم
الدرقية من تحت المهاد فيساعد على الحفاظ على
و الهرمون المنبه للغدة مستويات طبيعية لضغط
الدرقية من الغدة النخامية الدم و معدل ضربات
مشكال مسار تغذية القلب وقوة العضالت
راجعة مثبطة يمنع كما ينظم عمل الجهاز
االنتاج الزائد لهرمون الهضمي62و وظائف
الدرقية التكاثر
Disorders of Thyroid Function and
Regulation
• Hypothyroidism, too little thyroid
function, can produce symptoms such as
– Weight gain, lethargy, cold intolerance
• Hyperthyroidism, excessive production
of thyroid hormone, can lead to
– High temperature, sweating, weight loss,
irritability and high blood pressure
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Graves’ disease: مرض جريڤز
• The most common form of
hyperthyroidism in humans
• Protruding eyes (exophthalmos),
caused by fluid accumulation
behind the eyes, are a typical
symptom.
• In this autoimmune disorder, the body produces
antibodies that bind to and activate the receptor
for TSH, causing sustained thyroid hormone
production.
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Iodine deficiency:
• Iodine is essential for
thyroid hormone
biosynthesis.
• Insufficient dietary iodine
leads to an enlarged thyroid
gland, called a goiter تضخم
( الغدة الدرقيةone of the causes of goiter)
• The low blood levels of thyroid hormone are
insufficient to provide the usual negative
feedback on the hypothalamus and anterior
pituitary. 65
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• As a consequence, the
pituitary continues to
secrete TSH. Elevated
TSH levels cause an
enlargement of the
thyroid gland, resulting in
a swelling of the neck
known as goiter.
66
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Congenital hypothyroidism: قصور الغدة الدرقية الخلقي
• In humans, congenital hypothyroidism, an
inherited condition of thyroid deficiency,
• results in markedly retarded skeletal growth
and poor mental development.
• These defects can often be avoided, at least
partially, if treatment with thyroid hormone
begins early in life.
• Iodine deficiency in childhood causes the same
defects, but it is fully preventable if iodized
salt is used in food preparation.
67
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The fact that iodine in the
body is dedicated to the
production of thyroid
hormone provides a novel
diagnostic tool for
disorders of thyroid
function: Radioactive
forms of iodine enable
specific imaging of the
Thyroid scan. Physicians can
thyroid gland
use a radioactive isotope of
• Radioactive Iodine is iodine to detect abnormal
also used for treatment patterns of iodine uptake that
of some thyroid could indicate a thyroid disorder
disorders 68
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Hormonal Regulation of Growth
• Growth hormone (GH) is secreted by the
anterior pituitary gland and has tropic and
nontropic actions
• A major target, the liver, responds to GH by
releasing insulin-like growth factors (IGFs),
• IGFs circulate in the blood and directly
stimulate bone and cartilage growth.
• In the absence of GH, the skeleton of an
immature animal stops growing.
69
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Hormonal Regulation of Growth
• GH also exerts diverse metabolic effects that
tend to raise blood glucose levels, thus
opposing the effects of insulin.
70
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Pituitary dwarfism
• Retardation of long-bone Normal
72
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Gigantism
• Hypersecretion of GH during childhood
can lead to gigantism,
• In gigantism the person
grows unusually tall
but retains relatively
normal body
proportions
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Acromegaly
• Excessive GH production in adulthood
stimulates bony growth in the few body parts that
are still responsive to the hormone
• predominantly the face, hands, and feet.
• The result is an overgrowth of the extremities
called acromegaly (from the Greek acros,
extremity, and mega, large).
74
Concept 45.4: Endocrine glands respond
to diverse stimuli in regulating
homeostasis, development, and behavior
Parathyroid Hormone and Vitamin D: Control
of Blood Calcium
• Homeostatic control of blood calcium level is vital.
• Very low blood Ca2+ level cause skeletal muscles to
contract convulsively, a potentially fatal condition.
• If blood Ca2+ level are high, calcium phosphate
precipitates can form in body tissues, leading to
widespread organ damage.
75
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Parathyroid Hormone and Vitamin D:
Control of Blood Calcium
• Two antagonistic hormones regulate the
homeostasis of calcium (Ca2+) in the
blood of mammals
– Parathyroid hormone (PTH) is released
by the parathyroid glands
– Calcitonin is released by the thyroid
gland
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77
• PTH increases the level of blood Ca2+
– It releases Ca2+ from bone and stimulates
reabsorption of Ca2+ in the kidneys
– It also has an indirect effect, stimulating
the kidneys to activate vitamin D, which
promotes intestinal uptake of Ca2+ from
food
• Calcitonin decreases the level of blood
Ca2+
– It stimulates Ca2+ deposition in bones and
secretion by kidneys 78
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Adrenal Hormones: Response to Stress
• The adrenal glands are adjacent to the
kidneys
• Each adrenal gland actually consists of
two glands: the adrenal medulla (inner
portion) and adrenal cortex (outer portion)
79
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Catecholamines from the Adrenal Medulla
• The adrenal medulla secretes epinephrine
(adrenaline) and norepinephrine
(noradrenaline)
• These hormones are members of a class of
compounds called Catecholamines
• They are secreted in response to stress-
activated impulses from the nervous system
• They mediate various fight-or-flight
responses
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• Epinephrine and norepinephrine
– Trigger the release of glucose and fatty
acids into the blood
– Increase oxygen delivery to body cells
– Direct blood toward heart, brain, and
skeletal muscles, and away from skin,
digestive system, and kidneys
• The release of epinephrine and norepinephrine
occurs in response to involuntary nerve signals
81
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(a) Short-term stress response (b) Long-term stress response
and the adrenal medulla and the adrenal cortex
Stress
Nerve Hypothalamus
Spinal cord
signals
(cross section) Corticotropin Releasing
Nerve
hormone
cell Anterior pituitary
Blood vessel
Nerve cell ACTH
Adrenal medulla
secretes epinephrine
and norepinephrine. Adrenal cortex
secretes mineralo-
Adrenal corticoids and
gland glucocorticoids.
Kidney
85
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• Testosterone first
functions before
birth, promoting
development of
male reproductive
structures
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• Androgens play a major role again at puberty,
when they are responsible for the development
of male secondary sex characteristics.
• High concentrations of androgen lead to a low
pitch voice and male patterns of hair growth, as
well as increases in muscle and bone mass.
• Testosterone causes an increase in muscle and
bone mass and is often taken as a supplement
to cause muscle growth, which carries health
risks
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• Estrogens, most importantly estradiol, are
responsible for maintenance of the female
reproductive system and the development of
female secondary sex characteristics
• In mammals, progestins, which include
progesterone, are primarily involved in
preparing and maintaining the uterus to support
the growth and development of an embryo.
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• Estrogens and other gonadal sex hormones are
components of hormone cascade pathways.
• Synthesis of these hormones is controlled by
two gonadotropins from the anterior pituitary
gland, follicle-stimulating hormone and
luteinizing hormone.
• Gonadotropin secretion is in turn controlled by
GnRH (gonadotropin-releasing hormone),
from the hypothalamus.
89
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Endocrine Disruptors
• Between 1938 and 1971 some pregnant women
at risk for complications were prescribed a
synthetic, nonsteroidal estrogen analogue called
diethylstilbestrol (DES)
DES Estradiol
90
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Endocrine Disruptors
• DES is an endocrine disruptor, a molecule that
interrupts the normal function of a hormone
pathway, in this case, that of estrogen
• DES was given to pregnant women in the
mistaken belief it would reduce the risk of
pregnancy complications and losses.
• Daughters of women treated with DES are at
higher risk for reproductive abnormalities,
including miscarriage, structural changes, and
cervical and vaginal cancers
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Melatonin and Biorhythms
• The pineal gland, located in the brain,
secretes melatonin (modified amino acid;
tryptophan)
• Light/dark cycles control release of melatonin
• Primary functions of melatonin appear to
relate to biological rhythms associated with
reproduction and with daily activity levels
• Nightly increases in the levels of melatonin
play a significant role in promoting sleep.
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Melatonin Secretion by the Pineal Gland
Cytoskeletal
Systems Part 1:
MT
Lectures by
Kathleen Fitzpatrick
Simon Fraser University
–Microtubules
–Microfilaments
–Intermediate filaments
3
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Table 15-1 - Microtubules
4
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Table 15-1 - Microfilaments
5
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Table 15-1 – Intermediate Filaments
6
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Eukaryotes Have Three Basic
Types of Cytoskeletal Elements
• Indirect immunostaining has been used to
characterize cytoskeletal elements
7
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The Cytoskeleton Is Dynamically
Assembled and Disassembled
• The Cytoskeleton includes some remarkably
elaborate structures
• Microfilaments are essential components of muscle
fibrils
• Intermediate filaments provide structural support
and maintenance of animal cell shape
• Microtubules are structural elements of cilia and
flagella
8
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The Cytoskeleton Is Dynamically
Assembled and Disassembled
• Research has shown that the cytoskeleton is
dynamically assembled and disassembled
• Certain drugs can be used to perturb cytoskeletal
function
9
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The Cytoskeleton Is Dynamically
Assembled and Disassembled
• In this chapter, we will focus on the structure of the
cytoskeleton and how its components are
dynamically assembled and disassembled.
• In each case, we will consider
– the chemistry of the subunit(s),
– the structure of the polymer and how it is
polymerized,
– the role of accessory proteins, and
– some of the structural and functional roles each
component plays within the cell.
10
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Microtubules
• Microtubules are the largest of the cytoskeletal
components of a cell
• There are two types of microtubules involved
in a variety of functions in the cell:
1. Cytoplasmic microtubules pervade the
cytosol and are responsible for a variety of
functions
- Maintaining axons
- Formation of mitotic and meiotic spindles
- Maintaining or altering cell shape
- Placement and movement of vesicles
11
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Two types of microtubules (MTs)
• There are two types of microtubules involved
in a variety of functions in the cell:
2. Axonemal microtubules include the
organized and stable microtubules found in
structures such as
- Cilia
- Flagella
- Basal bodies to which cilia and flagella attach
• The axoneme, the central shaft of a cilium
or flagellum, is a highly ordered bundle of
MTs
12
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• Axonemal microtubules
Eukaryotic flagella.
1: Axoneme,
2: cell membrane,
3: IFT (Intraflagellar Transport)
4: basal body,
5: cross section of flagella,
6: triplets of microtubules of basal
body.
13
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Tubulin Heterodimers Are the Protein
Building Blocks of Microtubules
• MTs are straight, hollow cylinders of varied length
that consist of (usually 13) longitudinal arrays of
polymers called protofilaments
• The basic subunit of a protofilament is a
heterodimer of tubulin, one a-tubulin and one b-
tubulin
• These bind non-covalently to form an ab-
heterodimer, which does not normally dissociate
14
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Figure 15-2A Figure 15-2B
15
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Subunit structure
• a and b subunits have very similar 3-D structure,
but only 40% amino acid identity
16
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MT polarity and isoforms
• Because of dimer orientation, protofilaments
have an inherent polarity
17
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Microtubules Can Form as Singlets,
Doublets, or Triplets
• Cytoplasmic MTs are simple tubes, or singlet
MTs, with 13 protofilaments
19
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Microtubules Form by the Addition
of Tubulin Dimers at Their Ends
• MTs form by the reversible polymerization of
tubulin dimers in the presence of GTP and Mg2+
22
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Microtubule assembly
• The tubulin heterodimer concentration at
which MT assembly is exactly balanced with
MT disassembly is called the overall
critical concentration (Cc)
• At Critical concentration (Cc):
rate of polymerization = rate of
depolymerization
• Also, each end of the microtubule end has
its own critical concentration
23
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Addition of Tubulin Dimers Occurs
More Quickly at the Plus Ends of
Microtubules
• The two ends of a MT differ chemically, and one
can grow or shrink much faster than the other
• This can be visualized by mixing basal bodies
(structures found at the base of cilia) with tubulin
heterodimers
• The rapidly growing MT end is the plus end and
the other is the minus end
24
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Polar assembly of microtubules in vitro
• Basal body (an MTOC)
nucleates assembly of
microtubules from both
ends
• Plus end grows faster
than minus end
• Critical concentration
for the plus end is lower
than that for minus end
• Treadmilling is possible
25
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Treadmilling of microtubules
Treadmilling arises when a given tubulin molecule incorporated at the plus end is
displaced progressively along the MT and eventually lost by depolymerization at the
opposite end. 26
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Dynamic instability
• Dynamic instability model: one population of MTs
grows by polymerization at the plus ends whereas
another population shrinks by depolymerization
27
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GTP Hydrolysis Contributes to the
Dynamic Instability of Microtubules
– Each tubulin heterodimer binds two GTP molecules,
a-tubulin binds one and b-tubulin binds a second
28
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Dynamic instability
• Growing MTs have
GTP at the plus ends,
and shrinking MTs have
GDP
32
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Figure 15-8A,B
Microtubules originate
from the pericentriolar
material
33
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Nucleation and
assembly of MTs at a
centrosome in vitro
• In electron
micrographs of
the
centrosome,
MTs originate
from the
pericentriolar
material
34
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MTOCs Organize and Polarize the
Micotubules Within Cells
• MTOCs nucleate and anchor MTs
(A) Nerve cells contain two distinct sets of MTs, those of the axon and those of the dendrite.
Axonal MTs are attached at their minus ends to the centrosome, with their plus ends at the
tip of the axon. However, dendritic MTs are not associated with the centrosome and are of
mixed polarities.
(b) Ciliated epithelial cells have many MTOCs called basal bodies, one at the base of each
cilium. Ciliary MTs originate with their minus ends in the basal bodies and elongate with their
plus ends toward the tips of the cilia.
(c) Mature human red blood cells have no nucleus or MTOC. However, MTs of mixed
polarities persist as a circular band at the periphery of the cell. This band helps to maintain
the cell’s round, disk-like shape. pole. 37
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Figure 15-10D
(d) Throughout the process of mitosis, MTs in a dividing cell are oriented with their minus
ends anchored in the centrosome and their plus ends pointing away from the
centrosome.
Cell division is preceded by the division of the centrosome. The two centrosomes then
separate, each forming one pole of the mitotic spindle. At metaphase, the centrosomes
are at opposite sides of the cell. Each centrosome, or spindle pole, forms half of the
spindle MTs—some extending from pole to chromosomes, others extending from one
pole to the other
38
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Microtubule-Binding proteins
Microtubule-associated proteins (MAPs) act
as stabilizing and bundling proteins
• Tau cause microtubules to form tight
bundles in axons (MAP2: looser bundles
in dendrites)
39
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+-TIP: + end tubulin interacting proteins
stabilize the plus end preventing catastrophe,
Examples: Microtubules that reach to:
• Kinetochores
• Cell cortex
40
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Microtubule-Destabilizing/severing proteins
• Stathmin/Op 18 binds tubulin heterodimers
preventing them from polymerization
41
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Microtubule-Destabilizing/severing proteins
• Catastrophins (from the kinesin family of
proteins) binds the growing ends and induce
catastrophe
42
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Microtubule-Destabilizing/severing proteins
• Katanine severs MT
• It is named after the Japanese sword,
katana.
43
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Drugs Can Affect the Assembly of
Microtubules
44
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Colchicine
• Colchicine binds to tubulin monomers
forming Tubulin-Colchicine complex ,
inhibiting their assembly into MTs and
promoting MT disassembly
• The binding of colchicine to tubulin is slow, but
highly specific and essentially irreversible
• Tubulin-Colchicine complex can be added to
growing MT then prevent the addition of
further tubulin subunits and destabilizes the
structure promoting MT disassembly
45
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Colchicine
• tubulin is essential to mitosis, so colchicine
effectively functions as a "mitotic poison" or
spindle poison
– colchicine has been of great use in the
study of cellular genetics: to see the
chromosomes of a cell under a light
microscope.
46
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Colchicine
• colchicine also inhibits neutrophil motility
and activity, leading to a net anti-
inflammatory effect.
– useful in the treatment of
• Acute Gout flares.
• Familial Mediterranean fever (FMF)
47
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Nocodazole
48
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Vinblastine, vincristine
49
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Taxol
• Taxol binds tightly to microtubules and
stabilizes them, causing a depletion of free
tubulin subunits
50
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Antimitotic drugs
51
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Chapter 15
Cytoskeletal
Systems Part 2:
MFs and IFs
Lectures by
Kathleen Fitzpatrick
Simon Fraser University
55
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Microfilaments (MFs)
Contractile ( )اﻧﻘﺑﺎﺿﻲstructures
• Actin filaments together with myosin II
filaments form contractile structures in cells.
– the force is produced by ATP-driven
movement of the myosin II motor
domains along the actin filaments
– Examples: cytokinetic contractile ring,
myofibrils of muscle cells and stress
fibers of non-muscle cells.
56
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• Cell migration:
https://www.youtube
.com/watch?v=Qo4
VyOa069s57
Migration of mesenchymal stem cells in 2D culture
© 2012 Pearson Education, Inc.
• Cell migration: lamellipodia
https://vimeo.c
om/78962092
https://vimeo.co
m/78976186
https://www.youtube.com/watch?v=PsYpngBG394 60
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• Muscle contraction
• Requires
contractile
actomyosin
structures
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Cytokinesis:
HeLa LifeAct Cells
• the part of the cell Undergoing Mitosis
division process
during which the
cytoplasm of a
single eukaryotic
cell divides into two
daughter cells.
• cytokinetic
contractile ring
requires contractile HeLa cells stably expressing LifeAct (F-Actin)
actomyosin GFP and H2B mCherry.
https://www.youtube.com/watch?v=VtZx3H9vS_4
structures
62
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• Cytoplasmic streaming:
Cytoplasmic streaming in plant cells (Elodea)
https://www.youtube.com/watch?v=BB5rvjZzgFU
63
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Maintenance of cell shape: cell cortex
microfilaments
Amoeba In Motion
65
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Figure 15-12A
66
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Different Types of Actin Are Found
in Cells
• Actin is highly conserved, but there are some
variants
67
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Different Types of Actin Are Found
in Cells
• b- and g-actin localize to different regions of a cell
• In intestinal epithelial cells
– Apical end: b-actin
– Basal end: g-actin
68
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G-Actin Monomers Polymerize into
F-Actin Microfilaments
• G-actin monomers can polymerize reversibly into
filaments with a lag phase, and elongation
phase, similar to tubulin assembly
https://www.youtube.com/watch?v=VVgXDW_8O4U 70
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Demonstration of microfilament polarity
• Myosin subfragment 1 (S1) can be incubated with
microfilaments (MFs)
71
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Figure 15-13A,B
72
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Figure 15-13C
73
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Polarity of microfilaments
• The polarity of MFs is reflected in more rapid
addition or loss of G-actin at the plus end than
the minus end
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Stress fibers
83
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Proteins That Regulate Polymerization
• If the concentration of ATP-bound G-actin is high,
microfilaments will assemble until the G-actin is
limiting, however
• In the cell, a large amount of free G-actin is not
available because it is bound by thymosin b4
• Profilin competes with thymosin b4 for G-actin
binding
• When the profilin concentration is high,
polymerization is favored—but only if there are
free filament ends available.
84
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Proteins That Regulate Polymerization
No binding
No plus end growth
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Proteins That Regulate Polymerization
• ADF/cofilin is known to bind ADP-G-actin and
F-actin and is thought to increase turnover of
ADP-actin at the minus end of MFs.
• The ADP on these G-actin monomers can
then be exchanged for a new ATP, and the
ATP-G-actin can then be recycled for addition
to the growing plus ends of MFs.
• ADF/cofilin also severs filaments, creating
new plus ends in the process
86
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Proteins That Cap Actin Filaments
• Whether MFs can grow depends on whether
their filament ends are capped
88
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A sarcomere
(Greek sarx
"flesh", meros
"part") is the
basic unit of
striated
muscle
tissue.
89
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Proteins That Crosslink Actin Filaments
• Often, actin networks form as loose networks of
crosslinked filaments
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Proteins That Sever Actin Filaments
• MFs are broken up by proteins that sever and/or
cap them
• Gelsolin severs actin MFs and caps the newly
exposed plus ends, preventing further
polymerization
92
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Proteins That Bundle Actin Filaments
• Some actin-containing structures can be highly
ordered
94
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Crosslinks
• The MFs are connected to the plasma
membrane by crosslinks made of myosin I and
calmodulin
95
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Figure 15-17
96
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Figure 15-18
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Cell Signaling Regulates Where and When
Actin-Based Structures Assemble
• Cytoskeleton is highly changeable and dynamic
• Cell signaling regulates the activity of actin-
binding proteins which regulate the types of
actin-based structures that cells assemble
• Both plasma membrane lipids and several small
G proteins related to Ras regulate the formation,
stability, and breakdown of MFs.
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Cell Signaling Regulates Where and When
Actin-Based Structures Assemble
• In response to PDGF, fibroblasts will begin to grow,
divide, and form actin-rich membrane extensions that
resemble lamellipodia.
• Other factors, such as lysophosphatidic acid (LPA),
induce cells to form stress fibers.
• Many of these signals result in changes in the actin
cytoskeleton through their action on a family of
monomeric G proteins known as Rho GTPases (a
family of monomeric G proteins).
• Three key members of this family are Rho, Rac, and
Cdc42.
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Rho family of small GTPases regulates complex
actin-based structures:
Rho: Responsible for Control Rho
Cdc42 Rac
103
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Cell signalling regulates complex actin-based
structures
105
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Figure 15-22
107
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Classes of intermediate filament proteins
(continued)
• Class III: includes vimentin (connective tissue),
desmin (muscle cells), and glial fibrillary acidic
(GFA) protein (glial cells)
• Class IV: These are the neurofilament (NF)
proteins found in neurofilaments of nerve cells
• Class V: includes the nuclear lamins A, B, and C
that form a network along the inner surface of the
nuclear membrane
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Classes of intermediate filament proteins
(continued)
• Class VI: Neurofilaments in the nerve cells of
embryos are made of nestin
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Table 15-4
110
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Intermediate Filaments Assemble
from Fibrous Subunits
• IF proteins are fibrous rather than globular
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Intermediate filament assembly
• The basic structural unit consists of two IF
polypeptides intertwined into a coiled-coil
113
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Intermediate Filaments Confer
Mechanical Strength on Tissues
• IFs are important structural determinants in
many cells and tissues; they are thought to have
a tension-bearing role
115
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Integration of cytoskeletal elements
• Plakins are linker proteins
that connect intermediate
filaments, microfilaments,
and microtubules
• One plakin, called plectin,
is found at sites where
intermediate filaments
connect to MFs and MTs
116
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Chapter 16
Cellular Movement:
Motility and
contractility
Lectures by
Kathleen Fitzpatrick
Simon Fraser University
3
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Two eukaryotic motility systems
1. Microtubule-based movement
– Interactions between motor proteins and
microtubules
– E.g., fast axonal transport in neurons, or the sliding of
MTs in cilia and flagella
2. Microfilament-based movement
– Interactions between actin and members of the
myosin motor proteins
– E.g., muscle contraction
4
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Intracellular Microtubule-Based
Movement: Kinesin and Dynein
• MTs provide a rigid set of tracks for transport of a
variety of organelles and vesicles
6
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MT Motor Proteins Move Organelles
Along Microtubules During Axonal
Transport
• Proteins and neurotransmitters produced in the cell
body must be transported to the nerve ending
8
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Figure 16-2
9
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Motor Proteins Move Along
Microtubules by Hydrolyzing ATP
• Kinesins consist of three parts
11
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Figure 16-3A
12
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13
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Kinesin movement along MTs
15
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Dyneins Can Be Grouped into Two
Major Classes: Axonemal and
Cytoplasmic Dyneins
• Cytoplasmic dynein moves toward the minus
ends of MTs
17
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Microtubule Motors Are Involved in
Shaping the Endomembrane System
and Vesicle Transport
• MT motors are important for dynamically shaping
the complicated endomembrane system
18
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Figure 16-5
19
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Microtubule-Based Motility: Cilia and
Flagella
• Microtubules are required for movements of cilia
and flagella, the motile appendages of eukaryotic
cells
20
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Cilia and Flagella Are Common Motile
Appendages of Eukaryotic Cells
• Cilia: are about 2–10 µm long and occur in large
numbers on the surface of ciliated cells
21
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Figure 16-6A, B
22
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Cilia and flagella
23
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24
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Cilia and Flagella Consist of an
Axoneme Connected to a Basal Body
• Cilia and flagella share a common structure, the
axoneme
26
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Figure 16-7
27
© 2012 Pearson Education, Inc.
Figure 16-8B
28
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Structure of cilia and flagella
29
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Tubule structure
2- All of the tubules contain both tubulin and
tektin
30
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Axonemal dynein
32
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Figure 16-8C
33
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Microtubule Sliding Within the
Axoneme Causes Cilia and Flagella
to Bend
• The sliding-microtubule model suggests that
sliding of MTs relative to each other is converted
into localized bending because the doublets are
connected to the central pair and to each other
35
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Crosslinks and Spokes Are
Responsible for Bending
• Resistance in bending is provided by the radial
spokes that connect the doublets to the central pair
39
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Primary cilia
• Primary cilia are used in sensory structures
• These have a “9+0” structure, i.e., lacking the
central pair
• Not involved in motility but work as sensory
receptors
• Plays an important role in animal embryos during
their development
• Primary cilia in endothelial cells plays an important
role in the production of the potent vasodilator,
nitric oxide (NO)
40
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Actin-Based Cell Movement:
The Myosins
• Movements of molecules and other cellular
components also occur along another
system in the cell—the actin cytoskeleton
41
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Myosins Are a Large Family of Actin-
Based Motors with Diverse Roles in
Cell Motility
• Myosins are ATP-dependent motors that exert
force on actin filaments
43
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Figure 16-9
44
© 2012 Pearson Education, Inc.
The myosins
46
© 2012 Pearson Education, Inc.
Myosin functions
ØMuscle contraction
ØCell movement
ØPhagocytosis
ØVesicle transport
47
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Type II myosins
49
© 2012 Pearson Education, Inc.
Kinesins vs. myosin
• Kinesins operate alone or in small numbers to
transport vesicles over large distances
51
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Skeletal Muscle Cells Contain Thin
and Thick Filaments
• Skeletal muscles are responsible for voluntary
movement
52
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Skeletal muscle cells
• Multinucleate cells arise from fusion of embryonic cells
called myoblasts
– Results in multinucleated cell called syncytiums
55
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Figure 16-12a
56
© 2012 Pearson Education, Inc.
57
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Structure of A bands and I bands
60
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Thick Filaments
• Each thick filament consists of hundreds of
molecules of myosin, oriented in opposite
directions making the two halves of the filament
Diameter 15 nm 7 nm
Length 1.6 μm 1 μm
61
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Thin Filaments
• Thin filaments interdigitate with the thick
filaments
65
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Organization of Muscle Filament
Proteins
• The actin in thin filaments is oriented so that all the
plus ends are anchored at Z lines
67
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a-actinin is found in the Z disk
68
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Structural proteins associated with
thick filaments
• nebulin links thin filaments to Z line and stabilizes
the thin filament organization
– it is believed that nebulin acts as a thin filament
"ruler" and regulates thin filament length during
sarcomere assembly
• Myomesin is present at the H zone and bundles
the myosin molecules
• Titin attaches the thick filaments to the Z lines
and keeps thick filaments in correct position
relative to thin filaments during contraction
69
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Figure 16-15
70
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Table 16-2
71
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The Sliding-Filament Model Explains
Muscle Contraction
• The sliding filament model was proposed in 1954
72
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Figure 16-16A
73
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Muscle contraction
74
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Figure 16-16B
75
© 2012 Pearson Education, Inc.
76
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Cross-Bridges Hold Filaments Together
and ATP Powers Their Movement
Cross-Bridge Formation
77
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Cross-Bridge Formation
78
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Muscle contraction
• Muscle contraction is the net result of myofibril
shortening:
80
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The contraction cycle
81
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The contraction cycle (continued)
82
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Figure 16-18
Rigor Mortis
83
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The Regulation of Muscle Contraction
Depends on Calcium
• Most skeletal muscles spend more time in the
relaxed state than in contraction
84
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The Role of Calcium in Contraction
• The regulatory proteins tropomyosin and troponin
regulate the availability of myosin binding sites on
actin filaments in a calcium-dependent manner
86
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Figure 16-18
https://www.youtube.com/watch?v=p8iKzWqUU2s
87
© 2012 Pearson Education, Inc.
Regulation of Calcium Levels in
Skeletal Muscle Cells
• Calcium levels are controlled by nerve impulses
from motor neurons
88
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Events at the Neuromuscular Junction
90
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https://www.youtube.com/watch?v=7MSDS6jKJSA
91
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Transmission of an Impulse to the
Interior of the Muscle
• Membrane depolarization spreads through the
sarcolemma via the transverse (T) tubule
system
93
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SR Function in Calcium Release
and Uptake
• The SR has two functional components
96
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Terminal cisternae and calcium
97
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Figure 16-21
98
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Figure 16-21
99
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Muscle relaxation
100
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The Coordinated Contraction of
Cardiac Muscle Cells Involves
Electrical Coupling
• Cardiac muscle is responsible for the beating of
the heart
102
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Cardiac muscle
104
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The Structure of Smooth Muscle
• Smooth muscle cells are long and thin with
pointed ends; there are no striations
• Instead of Z lines, smooth muscles have dense
bodies, plaque-like structures
• Bundles of actin filaments are anchored to the
dense bodies in a crisscross pattern that runs
obliquely to the axis of the cell
• Dense bodies are also held in place and
connected to each other by IFs
105
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Figure 16-23A
106
© 2012 Pearson Education, Inc.
Figure 16-23B
107
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Regulation of Contraction in Smooth
Muscle Cells
• In response to nerve or hormonal signal,
extracellular calcium enters the smooth muscle
cell
108
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Myosin light-chain phosphorylation
109
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Figure 16-24A
110
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After contraction
111
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Actin-Based Motility
in Nonmuscle Cells
• Actin and myosin have been discovered in nearly
all eukaryotic cells
112
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Cell Migration via Lamellipodia Involves
Cycles of Protrusion, Attachment,
Translocation, and Detachment
• MFs are required for the movement of most cells
in animals
113
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Figure 16-25
114
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Extending Protrusions
115
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Extending filopodia followed by
lamellipodia
116
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Cell Attachment
• Attachment, or adhesion,
of the cell to the substrate
is necessary for cell
movement
• New sites of attachment
are formed at the front of
the cell
• Attachment sites are
complex structures
involving a number of
proteins
117
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Translocation and Detachment
• Contraction at the
rear of the cell
squeezes the
cell body forward
and releases the
attachments at the
rear
https://vimeo.co
m/78976186
120
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Amoeboid Movement Involves Cycles
of Gelation and Solation of the Actin
Cytoskeleton
• Amoebas and white blood cells exhibit a type of crawling
called amoeboid movement, which is accompanied by
protrusions of pseudopodia
122
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Figure 16-27
123
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• Amoeboid movement: WBCs
https://phys.org/news/2010-05-biologists-unravel-mechanisms-immune-cells.html
124
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Actin-Based Motors Move Components
Within the Cytoplasm of Some Cells
125
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Figure 16-28A
126
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Cytokinesis:
HeLa LifeAct Cells
• the part of the cell Undergoing Mitosis
division process
during which the
cytoplasm of a
single eukaryotic
cell divides into two
daughter cells.
• cytokinetic
contractile ring
requires contractile
HeLa cells stably expressing LifeAct
actomyosin (F-Actin) GFP and H2B mCherry.
structures https://www.youtube.com/watch?v=VtZx3H9vS_4
127
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Cell division: Mitosis and Meiosis
Selected Topics
1
Regulation of Cell Division
• A multicellular organism needs to coordinate cell
division across different tissues and organs
– for normal growth, development and maintenance
cell division has to occur at the appropriate times
and in the appropriate places.
• controlled timing of cell division
• controlled rates of cell division
– If cell division proceed inappropriately (e.g., cells
divide uncontrollably), pathological conditions like
cancer can result.
2
Regulation of Cell Division
• Frequency of cell division varies by cell type
– Embryo (ex:fly): cell cycle < 20 minute
– Skin cells: divide frequently throughout life
(12-24 hours cycle)
– Liver cells
• Stay in G0 but retain ability to divide
• divide once every year or two
– Mature nerve cells & muscle cells
• do not divide at all after maturity
• permanently in G0
3
Regulation of Cell Division
• Cells must accomplish two basic things during
the cell division:
– Copying cellular components
– Dividing the cell so that components are distributed
appropriately to the daughter cells
• The alternating “growth” and “division”
activities of the cell is called the “cell cycle”.
• The division activity corresponds to “M phase”.
• The “growth” activity corresponds to
“Interphase”.
4
Phases of the Cell Cycle
• The cell cycle consists of
– Interphase: cell growth and copying of
chromosomes in preparation for cell division
• longest phase: about 90% of the cell cycle
• divided into sub-phases .
– G1 phase (“first gap”)
– S phase (“synthesis”)
– G2 phase (“second gap”)
• The cell grows during all three phases, but
chromosomes are duplicated only during the S
phase 5
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• Mitotic (M) phase (mitosis and cytokinesis)
– Mitosis is conventionally divided into five phases
• Prophase
• Prometaphase
• Metaphase
• Anaphase
• Telophase
– Cytokinesis overlaps the latter stages of mitosis
6
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Figure 12.6
INTERPHASE
S
G1
(DNA synthesis)
s is
e
k in G2
s is
t o
y
to
MIT C
Mi
(M) O
PHA TIC
SE
7
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Duration of the Cell Cycle
• Time for a complete cell cycle varies greatly,
• Typical mammalian cell takes 24 hours
– G1: 5-6 hours
– S phase: 10-12 hours (about half of the cycle)
– G2: 4-6 hours
– M phase takes only about an hour
• Most variation in length of G1
– Resting phase G0 – cells spend more or less time
here
8
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Control of the Cell Cycle
• Current view integrates 2 concepts
1.Cell cycle has two irreversible points
– Replication of genetic material
– Separation of the sister chromatids
2.Cell cycle can be put on hold at specific
points called checkpoints
– Process is checked for accuracy and can be
halted if there are errors
– Allows cell to respond to internal and external
signals
9
Checkpoint control system
• cell cycle controlled by STOP & GO
chemical signals at critical points
• signals indicate if
key cellular
processes have
been completed
correctly
10
11
Checkpoint control system
3 major checkpoints:
1. G1/S checkpoint
– Cell “decides” to divide
– Primary point for external signal influence
2. G2/M checkpoint
– Cell makes a commitment to mitosis
– Assesses success of DNA replication
3. Late metaphase (spindle or M) checkpoint
– Cell ensures that all chromosomes are attached
to the spindle
12
G1/S checkpoint
• primary decision point and the most critical “Called
Restriction point in mammals and Start in yeast”
• a cell checks whether internal and external conditions are
right for division.
– Size. Is the cell large enough to divide?
– Nutrients. Does the cell have enough energy reserves or
available nutrients to divide?
– Molecular signals. Is the cell receiving positive cues (such
as growth factors, supportive extracellular matrix) from
neighbors?
– DNA integrity. Is any of the DNA damaged?
13
G1/S checkpoint
• if the cell receives “GO” signal, it becomes
irreversibly committed to division and it
divides
• if cell did not receive “GO” signal, it exits cycle
and switches to G0 phase
– non-dividing, working state
14
G0 phase
• non-dividing, differentiated state
• most human cells in G0 phase
• liver cells
– in G0, but can be
“called back” to cell
cycle by external cues
• nerve & muscle cells
– highly specialized
– arrested in G0 & can
G 0 never divide 15
G2/M checkpoint
• To make sure that cell division goes smoothly
(produces healthy daughter cells with complete,
undamaged DNA), the cell has G2/M checkpoint
before M phase.
• At this stage, the cell will check:
– DNA integrity. Is any of the DNA damaged?
– DNA replication. Was the DNA completely copied
during S phase?
16
G2/M checkpoint
• If the checkpoint mechanisms detect problems with the
DNA quantity (complete replication) or quality
– the cell cycle is halted, and the cell attempts to either
complete DNA replication or repair the damaged DNA.
17
G2/M checkpoint
• If no DNA problems were detected the cell receives a
“GO” signal and enter mitosis. The checkpoint
mechanisms activates proteins involved in:
– Chromosome condensation
– Nuclear envelope breakdown
– Spindle assembly
– Targeted protein degradation
18
Spindle or (M) checkpoint
• Because the separation of the sister chromatids during
anaphase is an irreversible step, the cycle will not proceed
until all the chromosomes are firmly attached to at least
two spindle fibers from opposite poles of the cell
• Before anaphase the cell monitors whether all the sister
chromatids are attached to the spindle microtubules.
– The kinetochores are the structures that are monitored
– Unattached kinetochores sustains the production of
signals (for example: Mad2, Mitotic Arrest-Deficient
2) which delays anaphase allowing time for the spindle
to capture the unattached chromosomes
19
Influenced by:
• DNA damage
• DNA replication
20
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The Cell Cycle Control System
• The sequential events of the cell cycle are
directed by a distinct cell cycle control system,
• The cell cycle control system is regulated by both
internal and external controls
• The system of switches is binary (ON/OFF) and
guarantees that at specific checkpoints, the cell
cycle stops until a go-ahead signal is received
21
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Cyclically activated protein kinases control
cell cycle progression
Cyclin-dependent kinases (Cdks)
• Enzymes that phosphorylate proteins triggering cell
cycle events
• Primary mechanism of cell cycle control
• Cdks expression is constant through the cell cycle
• Their kinase activity oscillates in the cell cycle
• Cyclical changes in Cdk activity are controlled by an
array of enzymes and other proteins, mainly Cyclins
22
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Cyclins:
• Cyclins are proteins whose levels rise and fall
during the various phases of the cell cycle
– cyclins, so named because their concentrations
vary with the cell cycle
• As said before, cyclins are the main regulators
of Cdks
– Interact with and activates cdks
– Cdks must bind to cyclins to be activated
– the periodic synthesis and destruction of cyclins
acted as a clock
23
Cyclin-CDK complexes
25
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There are two main groups of cyclins:
• G1/S cyclins – essential for the control of the cell cycle at
the G1/S transition,
• Cyclin D-Cdk4/6, and Cyclin E-Cdk2 – regulates
transition from G1 to S phase
• Cyclin A-Cdk2 – active in S phase, required to initiate
replication
• G2/M cyclins – essential for the control of the cell cycle at
the G2/M transition (mitosis). G2/M cyclins accumulate
steadily during G2 and are abruptly destroyed as cells exit
from mitosis (at the end of the M-phase).
• Cyclin B-Cdk1 – regulates progression from G2 to M
phase. 26
G1/S cyclins (cyclin E) trigger Start or entry into cell cycle. S phase
cyclins (cyclin A) trigger DNA replication. M phase cyclins (cyclin B)
initiate spindle assembly and attachment of microtubules to
chromosomes. Lastly, the anaphase-promoting complex (APC)
destroys all cyclins and initiates separation of sister chromatids.
27
http://tbl.med.yale.edu/cell_growth_control_2020/reading.php
The cell cycle control system is regulated by both
internal and external controls
• Some external signals are growth factors (mitogens),
proteins released by certain cells that stimulate other
cells to divide
– For example, epidermal growth factor (EDF) platelet-
derived growth factor (PDGF) or stimulates the division
of human fibroblast cells in culture
• An example of an internal signal is that kinetochores
not attached to spindle microtubules send a
molecular signal that delays anaphase (correct
completion of previous step)
28
Growth factor signaling through the Ras pathway
crossing of G1/S checkpoint
• Some mitogens (see next figure) , such as epidermal
growth factor (EGF), increase the amount of cyclin D
by activating transcription of cyclin D.
• Mitogens bind receptors (often an RTK) that activates a
guanine nucleotide exchange factor for the small GTP-
binding protein Ras.
• Ras-GTP then activates a MAP kinase (Mitogen-
activated protein kinase) pathway that ultimately leads
to the activation of a set of transcription factors
including Myc.
29
http://tbl.med.yale.edu/cell_growth_control_2020/reading.php
Growth factor signaling through the Ras pathway
crossing of G1/S checkpoint
• Myc increases the transcription of cyclin D. Because
the receptor, Ras and Myc all regulate the expression of
cyclin D, mutation in these proteins that makes them
continuously active can lead to uncontrolled cell
division.
• For this reason the receptor, Ras and Myc are known as
Proto-oncogenes.
30
http://tbl.med.yale.edu/cell_growth_control_2020/reading.php
Growth factor signaling through the Ras pathway
crossing of G1/S checkpoint
31
http://tbl.med.yale.edu/cell_growth_control_2020/reading.php
Response to a growth factor (mitogen) and
cyclin-Cdk Mitogens bind receptors that trigger a signal
transduction pathway that leads to the activation
of cyclin D-Cdk4. Cyclin D-Cdk4 then triggers
the activation of Cyclin E-Cdk2 which triggers
entry into start and activation of Cyclin A-Cdk2.
Cyclin A-Cdk2 initiate DNA replication.
32
http://tbl.med.yale.edu/cell_growth_control_2020/reading.php
G2/M Checkpoint Control by MPF
• MPF (maturation-promoting factor) is a cyclin-Cdk
complex that triggers a cell’s passage past the G2
checkpoint into the M phase
• Active MPF = Mitotic Cdk + mitotic cyclin (Cyclin B)
• MPF controls G2 ® M by phosphorylating and
activating proteins involving in:
– Chromosome condensation
– Nuclear envelope breakdown
– Spindle assembly
– Targeted protein destruction (itself and others)
33
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G2/M checkpoint
M G1 S G2 M G1 S G2 M G1
MPF activity
Cyclin
concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration 34
during the cell cycle
Spindle assembly checkpoint controls
Metaphase to Anaphase transition
• MPF also activates anaphase-promoting
complex/cyclosome (APC/C):
• Active APC/C is required to trigger anaphase as well
as for the exit from mitosis
• Activates sister chromatid separation
• APC targets some proteins for degradation
• Unattached kinetochores relay signals (recall: Mad2)
that inhibit the Anaphase promoting complex
(APC/C) thus delaying the anaphase until all
kinetochores are attached
35
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Spindle assembly checkpoint controls
Metaphase to Anaphase transition
36
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Spindle assembly
checkpoint controls
Metaphase to
Anaphase
transition
37
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The anaphase-promoting complex/cyclosome
(APC/C)
39
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How does the APC/C starts sister chromatid
separation?
• The APC/C trigger the separation of sister chromatids
during mitosis. If the APC/C gets the right signals at
metaphase, it sets off a chain of events that
destroys cohesin, the protein glue that holds sister
chromatids together
• APC will not start its work until the inhibitory
signals (Mad2) stops coming from kinetochore
MT’s.
– This signal stops once Kinetochores are all
attached to MT’s
40
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How does the APC/C starts sister chromatid
separation?
• Securin normally binds to, and inactivates, a protein
called separase.
43
Development of Cancer
• 6 key mutations (“hits”) are involved in the
development of cancer (the more hits the more
aggressive is the cancer)
1. Sustaining proliferative signaling: unlimited
growth
– turn on growth promoter genes
2. Evading growth suppressors: ignore
checkpoints
– turn off tumor suppressor genes (p53)
3. Resisting cell death: escape apoptosis
– turn off suicide genes
44
Development of Cancer
4. Enabling replicative immortality: unlimited
divisions
– turn on chromosome maintenance genes
5. Inducing angiogenesis: promotes blood vessel
growth
– turn on blood vessel growth genes
6. Activating invasion and metastasis: overcome
anchorage & density dependent inhibition
– turn off touch-sensor gene
• Depending on whether the affected gene normally
stimulates or inhibits proliferation, the mutated gene
is called an oncogene or a tumor-suppressor gene.
45
• Density-dependent inhibition: crowded cells stop
dividing as a consequence of cell-cell contact:
– Example: Fibroblasts
• Anchorage dependence inhibition, cells must be
attached to the right substratum (cells, extracellular
matrix, or tissue culture plastic) via proteins in
order to divide
– Example: Epithelial cells
• Metastatic cancer cells exhibit neither density-
dependent inhibition nor anchorage dependence
46
Tumor-suppressor genes
• A tumor suppressor gene, is a gene that codes
for a protein that protects a cell from one step
on the path to cancer.
• First tumor-suppressor identified was the
retinoblastoma susceptibility gene (Rb)
– Predisposes individuals for a rare form of cancer
that affects the retina of the eye
• p53 gene is another example
47
Tumor-suppressor genes
• p53 plays a key role in G1 checkpoint
• p53 protein monitors integrity of DNA
– If DNA damaged, cell division halted and repair enzymes
stimulated
– If DNA damage is irreparable, p53 directs cell to kill itself
• p53 is essential for stopping cells with damaged DNA
from entering S phase.
– Prevent the development of mutated cells
containing mutations
• p53 is absent or damaged in many cancerous cells
48
Proto-oncogenes
• Normal cellular genes that become oncogenes when
mutated
– Oncogenes can cause cancer
• Some encode receptors for growth factors (HER2)
– If receptor is mutated in “on”, cell no longer depends on
growth factors
• Some are signal transduction proteins (See before:
Ras)
• Some are transcription factors: (See before: Myc)
49
Ethical issues in cell biology
• THE USE OF HUMAN BIOLOGICAL
MATERIAL
• Human biologic material has been widely used for a
long period for laboratory diagnostics in biochemistry,
haematology, immunology, histopathology, molecular
genetics, and cytopathology.
• The abuse of human biologic material concerns mainly
reproductive biology and human cloning. Long-term
experience has led to the formulation of widely
accepted laws and regulations in many countries
50
Ethical issues in cell biology
• THE USE OF HUMAN BIOLOGICAL
MATERIAL
• To eliminate risk, the use of human biologic samples
for research and therapeutic cloning must subordinate
the informed acceptance of the donor and their use
for reproductive cloning is forbidden. Diverse
cultural meanings are associated with biologic
material which is considered waste tissue, typically
the placenta.
51
Ethical issues in cell biology
• The Story of Henrietta lacks
https://www.bionews.org.uk/page_159684
Major discoveries using Hela Cells (for the next
lecture)
52
The Nucleus during cell division (self study)
The Nuclear envelope (NE)
• NE is composed of:
• Outer (ONM): contiguous with the ER and contain
many of the same ER proteins and lipids
• Inner membrane (INM): distinct, contains at least
100 unique components and may contain over 1000
proteins, many of which interact with chromosomes
and/or the nuclear lamina
• The ONM and the INM are separated by a perinuclear
space (20–40 nm)
53
The Nuclear envelope (NE)
Nuclear envelope:
Inner membrane
Outer membrane
Nuclear pore
Rough ER
Nuclear pore
complex
Surface of nuclear
envelope Ribosome
Close-up
0.25 µm
of nuclear Chromatin
envelope
1 µm
Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Nucleus
during Mitosis. 58
The Nucleus during Mitosis
• The nucleus disassembles and re-forms each time
most cells divide.
• At the beginning of mitosis, the chromosomes
condense (prophase) and the nuclear envelope
fragments (prometaphase), resulting in the release
of most of the contents of the nucleus into the
cytoplasm.
• At the end of mitosis, the process is reversed (not
just a simple reversal of events): The chromosomes
decondense, and nuclear envelopes re-form around
the separated sets of daughter chromosomes.
59
Nuclear envelope breakdown (NEBD)
• NEBD begins with tearing and stretching of the
NE by microtubules and the motor protein dynein.
• Upon phosphorylation by mitotic kinases, the
nuclear lamina disassembles and the Integral
nuclear membrane proteins detach from the
chromatin.
• The nuclear membrane and its integral membrane
proteins then disperse throughout the ER, whereas
the peripheral nuclear membrane proteins become
cytosolic.
Chen, R.-H. 2012. Nuclear Envelope Assembly and Disassembly During the Cell Cycle. eLS. . 60
The tearing force from microtubules
64
• CDK1 might also be directly involved in NPC
disassembly by phosphorylating many of their protein
components
• Also, the release of Integral nuclear membrane
proteins (INM proteins) from lamins and chromatin
might depend on CDK1 phosphorylation
• Güttinger S et al, “Orchestrating nuclear envelope disassembly and reassembly during mitosis.”
Nat Rev Mol Cell Biol. 2009 Mar;10(3):178-91. doi: 10.1038/nrm2641.
• Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates;
2000. The Nucleus during Mitosis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9890/
• Chen, R.-H. 2012. Nuclear Envelope Assembly and Disassembly During the Cell Cycle. eLS. .
65
Nuclear Envelope Assembly
66
Nuclear Envelope Assembly
The nuclear envelope reassembles by sequential
targeting of envelope components to the chromatin
surface,
1. This begins with attachment of membrane vesicles
containing some integral NE proteins
2. These proteins help in recruiting lamins to the
reforming nucleus. (Lamin dephosphorylation is
required for nuclear lamina reassembly)
3. Lamins repolymerize around the daughter cell
chromatin and the nuclear envelope is
reconstructed.
4. Chromatin decondensation then follows
67
Chen, R.-H. 2012. Nuclear Envelope Assembly
and Disassembly During the Cell Cycle. eLS. .
68
Centrosome Duplication is Tightly Coordinated
with Cell Cycle Progression (self study)
• A centrosome is composed of two, barrel-shaped
centrioles embedded in an amorphous proteinaceous
matrix, known as the pericentriolar material (PCM)
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Holland AJ et al, Centriole duplication: A lesson in self-control. Cell Cycle. 2010;9(14):2731-2736. doi:10.4161/cc.9.14.12184.
Centrosome Duplication is Tightly Coordinated
with Cell Cycle Progression
• Like DNA, centrosome duplication is a semi-
conservative process that occurs once, and only once,
per cell cycle.
• Centrosomes and chromosomes are the only
structures that are known to be precisely duplicated
and partitioned equally during each cell division.
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Holland AJ et al, Centriole duplication: A lesson in self-control. Cell Cycle. 2010;9(14):2731-2736. doi:10.4161/cc.9.14.12184.
Centrosome Duplication is Tightly Coordinated
with Cell Cycle Progression
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Holland AJ et al, Centriole duplication: A lesson in self-control. Cell Cycle. 2010;9(14):2731-2736. doi:10.4161/cc.9.14.12184.
The centriole replication cycle
1. Centriole replication occurs during S phase and is
marked by the formation of procentrioles at the
proximal end of each parental centriole.
2. As the cell progresses through S and G2 phases,
daughter centrioles elongate until they reach the
length of their parents.
• The mother and daughter centrioles are held
in an orthogonal (right angles) configuration
and the two pairs of centrioles remain
connected, functioning a single microtubule-
organizing center until late G2.
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Holland AJ et al, Centriole duplication: A lesson in self-control. Cell Cycle. 2010;9(14):2731-2736. doi:10.4161/cc.9.14.12184.
The centriole replication cycle
3. At the G2-M transition centrosome maturation occurs
and the centrosomes separate and instruct the formation
of the two spindle poles of the bipolar microtubule
spindle.
4. At anaphase, the microtubule spindle divides the
centrosomes such that each new daughter cell will
inherit one centrosome.
5. At the end of mitosis, centrioles lose their orthogonal
configuration in a process known as disengagement.
• It has been proposed that this step may be required to
license an additional round of centriole duplication
in the next cell cycle.
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Holland AJ et al, Centriole duplication: A lesson in self-control. Cell Cycle. 2010;9(14):2731-2736. doi:10.4161/cc.9.14.12184.
Spermatogenesis and
Oogenesis (self study)
74
Spermatogenesis
Epididymis Seminiferous
Sertoli cell
tubule nucleus
Spermato-
gonium
Primary
Testis spermatocyte
Cross section of
seminiferous tubule Secondary
spermatocyte
• Production of sperm Spermatids
(two stages)
– Continuous
• Occurs in the testes Sperm cell
Lumen of
– Seminiferous tubules seminiferous tubule
75
What happens is …
• Spermatogonia (stem cells that give rise to sperm)
are located at the periphery of each seminiferous
tubule
– Spermatogonia are diploid
• Developing sperm move toward the central
opening (lumen) of the tubule as they undergo
meiosis and differentiation
• 4 cells result
– Develop into mature sperm
– Haploid
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Spermatogenesis Primordial germ cell in embryo
Mitotic divisions
Secondary spermatocyte n n
(haploid cells with
duplicated Chromosomes) Meiosis II: Few hours
Early spermatid n n n n
haploid cells with
unduplicated Chromosomes Differentiation (24 days)
(Sertoli cells
provide nutrients)
Sperm cell n n n n
Campbell
77
Oogenesis
• The development of ova
– Mature, unfertilized eggs cells
– Happens in the ovary
• Oogonia (stem cells that give rise to ova)
– Multiply and begin meiosis
– STOPS at prophase 1
– At this phase, the cells are called primary oocytes
– Remain in this phase until the onset of puberty,
when they are activated by hormones
• Activated by LH and FSH
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What happens next ...
• Beginning at puberty, FSH periodically
stimulates a follicle to grow and induces its
primary oocyte to complete meiosis I and start
meiosis II
• Meiosis II then STOPS again
– The secondary oocyte, released during ovulation,
does not continue meiosis right away (arrested at
Metaphase of Meiosis 2)
– Penetration of the egg cell by sperm triggers the
completion of meiosis
– Then meiosis II is complete
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Oogenesis Primordial germ cell
Mitotic divisions
In embryo
2n Oogonium
(diploid)
Mitotic divisions
Completion of meiosis II
Second (Stimulated by fertilization)
polar n
body Fertilized egg (before the two nuclei fuse each one
n is haploid with unduplicated chromosomes. Fusion
produces a diploid zygote with unduplicated 80
Campbell chromosomes)
Major differences between Spermatogenesis
and Oogenesis
1. Unevenness in the mitotic division/cytokinesis
of oogenesis
– Almost all the cytoplasm à 1 daughter cell
(secondary oocyte) and 3 polar bodies which
degenerate
– Spermatogenesis = four mature sperm
2. The cells that produce sperm continue to divide
by mitosis throughout life (males)
– Not the case for women (born with all the primary
oocytes ) 81
Major differences between Spermatogenesis
and Oogenesis
3. Resting periods:
– Oogenesis has long resting periods
– Sperm is produced in an uninterrupted sequence
• During oogenesis centrioles are completely
degenerated, while sperms keep one centriole
while partially degrade the other and use it in
the formation of the flagellum
– (Oocyte centrosome reduction and division arrest at
different stages plays an important in preventing
parthenogenetic embryogenesis ( )ﺗﻛﺎﺛر ﻋذريand balancing
centrosome number in the embryonic cells.) 82