CELL JUNCTIONS, CELL

ADHESION MOLECULES

Cell Signaling and Communication

 Cell communication
• Cell to cell communication is important for multicellular organisms

• Multicellular organisms can be thought of as behaving as

community
• Trillions of cells that make up an organism need to communicate with
each other so they can coordinate their activities.

• Just as in a family or community, a breakdown in communication

can have detrimental effects.

• Many metabolic disorders and cancers are a result of

malfunctioning among cells
 Cell communication

• Cells communicate by sending and receiving signals.

• Signals may come from the environment, or they may

come from other cells.

• Signal can be send through:

1. Contact with another cell (cell junction/cell adhesion)

2. molecules secreted into the extracellular space by
another cell
 Molecules that adhere cells

• There are four families of integral membrane proteins

that play a role in mediating cell-cell adhesion:

1. Selectins
2. Immunoglobulin superfamily
3. Cadherins
 Molecules that adhere cells :

Selectins

• Selectins are a family of integral membrane

glycoproteins that recognize and bind to
oligosaccharides that project from the surfaces of
other cells.
There are 3 types of selectins:
1. E-selectin, present on
Endothelial cells
2. P-selectin, present on
Platelets and endothelial cells
3. L-selectin, present on all
Leukocytes

• Selectin ensures that a

particular types of cells could
adhere to its original sites.
• EGF-like domain = Epidermal
growth factor-like domain
 Molecules that adhere cells: Immunoglobulin superfamily

• Immunoglobulin superfamily (IgSF)

• responsible to mediate the specific interactions of lymphocytes with other
cells
• required for an immune response e.g. macrophages, other lymphocytes
and target cells.
e.g: cell surface antigen
receptors, co-receptor,
cytokine receptor, etc

• There are also some IgSF member such as vascular cell-adhesion molecule
(VCAM), neural cell-adhesion molecule (NCAM) and L1 that mediate
adhesion between non-immune cells.
• The non-immune IgSF are important
for neuron formations.

• Without them the axon cannot grow

properly and may lead to mental
retardation or hydrocephalus.

• Hydrocephalus is the accumulation

of cerebrospinal fluid in the brain.
Molecules that adhere cells : Cadherins

• Large family of glycoproteins

• Cadherins (named for ‘ calcium dependent adhesion)
• mediate calcium-dependent cell adhesion and
transmit signals from the extracellular matrix (ECM)
to the cytoplasm.
• Play important roles in cell adhesion, forming
adherens junctions to bind cells within tissue
together.
Cadherins join cells
of similar type to
one another and do
so by binding to the
same cadherin
present of the
surface of the
neighboring cells.
Cell junctions

• With the help of selectins, IgSF and cadherins, cells

could have different types of junctions between them,
including:
1. Synapses
2. Adherens junctions
3. Desmosomes
4. Gap junctions
5. Tight junctions
6. Plasmodesmata
Cell junctions: Synapses
• Synapse/synaptic junctions are junctions that exist
between two neurons.

• The interactions between neurons are important for

the transmission of signals. However, it is important
that the neuron “select” the right neighboring
neurons to transmit the signal.

• This is accomplished by protocadherins found on the

end of the axons.
Protocadherins are
present in the center of
the synapse where they
mediate specificity in the
interaction between the
neurons.

Cadherins also needed to

provide adhesion between
the neurons.
Cell junctions: Adherens junctions
• Adherens junctions are common in epithelia tissues
where they occur as a “belt” that encircles each of
the cells near its surface, binding that cell to its
surrounding neighbors.
• The “belt” is made by cadherins and actins.
Cell junctions: Desmosomes
• Desmosomes are disk-shaped adhesive junctions that
are found in tissues specialized to deal with
mechanical stress such as cardiac muscle.
• Like adherens junctions, desmosomes contain
cadherins that link two cells together.
Cell junctions: Desmosomes
• There are two types of cadherins structures for desmosomes:
1. Desmogleins
2. Desmocollins

• A network of ropelike intermediate filaments provides tensile

strength to the sheet of cells.
• Cadherins are important to maintain the structure integrity,
without them people will suffer from pemphigus vulgaris
• Pamphigus vulgaris is an
autoimmune disorder.
• Involves autoantibodies against
desmosome proteins
• These antibodies break the bonds
between skin cells.
• This leads to the formation of
painful blister. 

• Autoimmune disorders:
• An autoimmune disorder occurs
when the body's immune system
attacks and destroys healthy body
tissue by mistake.
• There are more than 80 types of
autoimmune disorders.
 Cell junctions: Gap junctions
• Gap junctions are sites between animal cells that are specialized for
intercellular communications.
• The plasma membranes of adjacent cells come very close to one another
but do not actually touch. Instead, there are very fine strands between the
cells that pass through the plasma membranes into the cytoplasm.
• The gap junctions are composed entirely by an integral membrane protein
known as connexin.
• Small molecules and electrical signals in one cell can pass through
the gap junctions to adjacent cells
 Cell junctions: Tight junctions
• Tight junctions are located at the apical end of the junctional
complex between adjacent epithelial cells.
• The adjoining of epithelial cells membranes make contact at
intermittent points
• Tight junctions serve as barriers to the free diffusion of water and
solutes from the extracellular compartment on one side of the
epithelial sheet to that on the other side.
Summary of cell junctions in animals
 Cell junctions: Plasmodesmata
• Plant cells lack the specialized junctions found in animal tissues but
they are connected by plasmodesmata.

• Plasmodesmata are cytoplasmic channels that pass through the cell

walls of adjacent cells.
• Plasmodesmata are lined by plasma membrane and a contain a
dense central structure known as desmotubule

• Plasmodesmata (singular: plasmodesma)

Cell signaling system

• Cell signaling is the process where a cell responds to the

stimulus from its environment by relaying information to its
internal compartments.

• There are 3 stages in cell signalling:

1. Reception
2. Transduction
3. Response
There are 3 stages in cell signalling:
• In reception, a chemical signal binds to a cellular protein, typically at the cell’s
surface or inside the cell.
• In transduction, binding leads to a change in the receptor that triggers a series of
changes in a series of different molecules along a signal-transduction pathway.
The molecules in the pathway are called relay molecules.
• In response, the transduced signal triggers a specific cellular activity. Cell
signaling and response helps with cell coordination
Overview of cell signaling

EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane

1 Reception 2 Transduction 3 Response

Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway

Signal
molecule
• The signal transduction is a complex process involving signaling
pathways.

• Cell signaling could be controlled by:

1. Phosphorylation/dephosphorylation through protein
kinases and phosphatases
2. GTP-binding proteins (G-proteins). G protein is active when
it binds to a GTP but inactive when binds to GDP.
3. Accessory proteins that could regulate G protein activities.
• There are 3 types of accessory proteins including:
1. GTPase-activating proteins (GAP), GAP could stimulate G
protein to hydrolyze GTP.
2. Guanine nucleotide-exchange factors (GEFs), GEF could bind
to an inactive G protein and stimulate the release of GDP in
exchange for GTP so that GTP could bind to the G protein and
activate it
3. Guanine nucleotide-dissociation inhibitors (GDI), inhibit the
release of GDP from G protein thus maintaining the protein
in the inactive form
Important proteins and molecules for cell
signaling
• Many proteins and molecules are found to be important for
cell signaling including:
1. cAMP (second messenger)
2. G protein-coupled receptors and G proteins
3. Calcium
4. Receptor tyrosine kinases (RTK)
5. Nitric oxide (NO)
6. Phosphatases
7. And many more
 Important proteins and molecules for cell
signaling: cAMP
• Cyclic adenosine monophosphate (cAMP) is a second messenger.
• a substance that is released into the interior of the cell following the
binding of a first messenger (hormone or other ligand) to the receptor
at the outer surface of the cell.

• cAMP transferring into cells the effects of hormones like glucagon

and adrenaline, which cannot pass through the cell membrane.

• There are a lot of other second messengers besides cAMP.

• While first messenger is very specific to a single type of receptor, the

second messenger could trigger many reactions so the cells would
give a large scale, coordinated response.
The response of a liver cell to glucagon or epinephrine
(adrenalin)- general view of signal amplification

https://www.youtube.com/watch?v=ejq99wLEMTw
1. Epinephrine binds to signal receptor on
plasma membrane
2. The signal activates Adenylyl cyclase which
converts ATP to cAMP
3. cAMP binds to and activates protein kinase
A (PKA)
4. The activated Protein Kinase A
phosphorylates another enzyme called
phosphorylase kinase. Active
Phosphorylase kinase activates
phosphorylase
5. Phosphorylase converts glycogen to
glucose.
6. Epinephrine causes glucose to be released
into the blood during flight-or-fight situation
Amplification of signal In the same pathway in the previous slide, 1
molecule of epinephrine activates a series of
Reception
signal molecules including cAMP.
Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction The final activated protein is glycogen

Inactive G protein phosphorylase which convert glycogen to
Active G protein (102 molecules) glucose.
Inactive adenylyl cyclase
Active adenylyl cyclase (102) This pathway amplifies the signal…one
signal molecule can activate 100 molecules of
ATP
Cyclic AMP (104) G-protein, and so on…
Inactive protein kinase A
Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Response
Glycogen
Glucose-1-phosphate
(108 molecules)
In the signal transduction pathway, various types of cells may receive the same signal but
produce very different responses.
For example, epinephrine triggers liver or striated muscle cells to break down glycogen,
but stimulates cardiac muscle cells to contract, leading to a rapid heartbeat.
• The explanation for this specificity is that different kinds of cells have different
collections of proteins.
• The response of a particular cell to a signal depends on its particular collection of
receptor proteins, relay proteins, and proteins needed to carry out the response
Two cells that respond differently to the same signal differ in one or more of the
proteins that handle and respond to the signal.
G protein-coupled receptors

• G-protein-coupled receptors (GPCR) always work with the

help of G proteins.

• GPCR and G proteins transduct signals following this

sequence:
1. Activation of the G protein by the receptor
2. Relay of the signal from G protein to the effector
3. Ending the response.

https://www.youtube.com/watch?v=Glu_T6DQuLU

https://www.youtube.com/watch?v=6FE7kN_5bCw
 1. When signal molecule binds to G-protein receptor,
The receptor becomes active.
2. Then the receptor binds to G-protein. When it
G-protein-linked Receptor binds to G-protein, the GDP released and
replaced with GTP.
Signal-binding site
3. Now G-protein becomes active. The active G-
protein moves away and binds to the enzyme.
4. Enzyme becomes active. After the G-protein does
its job, it hydrolyzes GTP to GDP and now becomes
Segment that
interacts with
inactive.
G proteins

G-protein-linked Activated Inctivate

Plasma Membrane Signal molecule
Receptor Receptor enzyme

GDP
G-protein GDP GTP
CYTOPLASM (inactive) Enzyme

Activated
enzyme

GTP
GDP
Important proteins and molecules for cell signaling: Calcium
• Calcium ions are important to transduct signal for:
• muscle contraction,
• cell division,
• secretion,
• endocytosis,
• fertilization,
• synaptic transmission,
• metabolism
• cell movement.

• Calcium-induced calcium release (CICR) is a process that a calcium ion

triggers a release of a lot of calcium ions. This process amplifies the signal.
• CICR is commonly seen in excitable cells such as muscle and neurons.
 Important proteins and molecules for cell signaling:
Calcium
Calcium ions and Inositol Triphosphate (IP3)
• The Ca2+ concentration in the cytosol is typically much lower than that outside the cell.
• Various protein pumps transport Ca2+ outside the cell or into the endoplasmic
reticulum or other organelles.
• As a result, the concentration of Ca2+ in the ER is usually much higher than the
concentration in the cytosol.
• Because cytosolic Ca2+ is so low, small changes in the absolute numbers of ions
causes a relatively large percentage change in Ca2+ concentration.
Calcium is an important second messenger because cells are able to regulate its
concentration in the cytosol

EXTRACELLULAR Plasma
FLUID membrane

Ca2+
ATP pump
Mitochondrion

Nucleus

CYTOSOL

Ca2+
pump
Endoplasmic
ATP Ca 2+ reticulum (ER)
pump

Key High [Ca2+] Low [Ca2+]

Other second messengers such as inositol triphosphate and diacylglycerol can trigger
an increase in calcium in the cytosol

1 A signal molecule binds 2 Phospholipase C cleaves a 3 DAG functions as

to a G protein receptor, leading to plasma membrane phospholipid a second messenger
activation of phospholipase C. called PIP2 into DAG and IP3. in other pathways.

EXTRA-
Signal molecule
CELLULAR
(first messenger)
FLUID
G protein

DAG
GTP
G-protein-linked PIP2
receptor Phospholipase C IP3 https://
(second messenger) www.youtube.
IP3-gated com/watch?
calcium channel v=WQFGxQD6
VtY
Endoplasmic Various
Cellular
reticulum (ER) Ca 2+ proteins
response
activated
Ca2+
(second
messenger)

4 IP3 quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions
the cytosol and binds to an IP3– the ER (down their con- activate the next
gated calcium channel in the ER centration gradient), raising protein in one or more
membrane, causing it to open. the Ca2+ level in the cytosol. signaling pathways.
Other pathways regulate genes by activating transcription factors that turn genes on
or off

Growth factor Reception

Receptor

Phosphorylation
cascade
Transduction

CYTOPLASM

Inactive
transcription Active
factor transcription
factor Response
P
DNA

Gene

NUCLEUS mRNA
 Important proteins and molecules for cell signaling:
Receptor tyrosine kinases

• Tyrosine kinase is an enzyme that adds phosphate groups to

specific tyrosine residues on other proteins.
• Tyrosin kinase are involved in the control of cell growth and
differentiation.
• Phosphorylation could either activate or inactivate a protein.
• Different from G protein and GPCR, tyrosine kinase and its
receptor is actually within the same complex.
• The receptor part of the tyrosine kinase is located at the
outside of membrane while the enzymatic part is located
intra-membrane.
 An individual tyrosine-kinase receptor consists of several parts:
> An extracellular signal-binding site.
> A single alpha helix spanning the membrane.
> An intracellular tail with several tyrosines.

https://www.youtube.com/watch?v=Ia6OjvBazGE
https://www.youtube.com/watch?v=LT_ws4Xvj7M
• When a ligand binds to the outer receptor, the inner tyrosine
kinase would be activated and transfers phosphate groups to :
1. Specific tyrosine residues of the other tyrosine kinase of the
complex. This process known as autophosphorylation
2. Some tyrosine residues of a small family of soluble proteins
substrates. The phosphorylated substrates would then
activate a variety of down-stream effectors.
Receptor tyrosine kinases

2. When signal molecules bind to the receptor, it causes the two ‘monomers’
to associate closely with each other, forming a dimer.
Receptor tyrosine kinases

3. Dimerization activates the tyrosine kinase monomers. Each tyrosine

kinase adds a phosphate from ATP to the other tail.
Receptor tyrosine kinases

4. Now the receptor is fully activated. It is recognized by specific relay proteins.

The relay protein binds to the phosphorylated tyrosine and becomes
activated. Each activated relay protein triggers a transduction pathway leading
to a cellular response.
Important proteins and molecules for cell
signaling: NO
• Nitric oxide is an important molecule that enables
macrophages to destroy invading pathogens.
• Nitric oxide synthase is induced in macrophages and is part
of the normal inflammatory response.
• Reactions between nitric oxide and macrophage cytoplasm
would produce an oxidizing agent peroxynitrite which can
react with lipid, DNA and proteins thus killing pathogens.
• However, NO is only lethal when it is in high concentration.
In low concentration it is used as signaling molecules
because of its small and diffusive size.
• It is found that aorta could be relaxed when acetylcholine is
provided (ACh).
• However, the relaxation only occurs when the endothelial and
smooth muscles cells are intact.
• It is later found out that the endothelial cell is responsible to
receive the acethylcholine and transmit the signal to finally
produce NO.
• The NO would then diffuse into smooth muscle cells to
generate cGMP that leads to muscle relaxation
• Nitroglycerin
• drug use to treat chronic chest pain (angina).
• breakdown into nitric oxide, which increases blood flow to the heart by
vasodilation (widening of the blood vessels)
1. acetylcholine binds to a receptor on
the endothelial cell.
2. Binding of Ach to receptor causes
influx of Calcium ions into lumen of
endothelial cell
3. Calcium ion activates the enzyme
nitric oxide synthase to produce NO
from Arginine
4. Nitric oxide diffuses into the
smooth cells
5. and activates guanylyl cyclase
resulting in the synthesis of
cyclicGMP,
6. which induces muscle cell
relaxation and blood vessel dilation
Important proteins and molecules for cell
signaling: Phosphatases
• As mentioned before, protein kinases could either stimulate
or inhibit the activities of other proteins.
• The effects of protein kinases could be reversed by stripping
the phosphates off the proteins by phosphatases.
 Other proteins/molecules involved in cell
signalling….

• Peptide hormones
• Growth factors
• Eicosanoids
• Plant hormones