BS PUBLIC HEALTH

BIOLOGY LECTURE
WEEK NO. 1 - CHAPTER 11 - CELL COMMUNICATION

LESSON OUTLINE eukaryotes like yeasts and then were

adopted for new uses by their
I. Cellular Messaging multicellular descendants.
II. Cell Signaling Evolution ● Quorum sensing allows bacterial
III. Local & Long-Distance Signaling populations to coordinate their
IV. The Three Stages of Cell Signaling behaviors in activities that require a
V. Reception given number of cells acting
VI. Receptors in the Plasma synchronously.
Membrane ● Biofilms are an aggregation of
VII. Intracellular Receptors bacterial cells adhered to a surface.
VIII. Transduction Bacteria form biofilms in response to
IX. Response environmental stresses such as UV
X. Apoptosis radiation, desiccation, limited
nutrients, extreme pH, extreme
temperature, high salt
concentrations, high pressure, and
Cellular Messaging antimicrobial agents.
● Quorum sensing can cause a
● Cells can signal to each other and secretion of toxins by infectious
interpret the signals they receive bacteria. Interfering with the
from other cells and the signaling pathways used in quorum
environment. sensing represents a promising
● Apoptosis is a mechanism of approach as an alternative
programmed cell death that treatment.
integrates input from multiple
signaling pathways.

Local & Long-Distance Signaling

Cell Signaling Evolution ● Cell-cell recognition is a sort of

local signaling that is especially
● Unicellular yeast Saccharomyces important in embryonic
cerevisiae—which are used to make development and the immune
bread, wine, and beer—identify their response. It is a direct contact
sexual mates by chemical signaling. between membrane-bound
● Signal transduction pathway cell-surface molecules.
involves the binding of extracellular ● There are two types of signaling:
signaling molecules and ligands to local signaling and long-distance
receptors located on the cell surface signaling.
or inside the cell that trigger events ● Local signaling involves molecules
inside the cell, to invoke a response. that travel only short distances; such
● Scientists think that signaling local regulators influence cells in the
mechanisms first evolved in ancient vicinity.
prokaryotes and single-celled a. Paracrine Signaling: A
signaling cell acts on nearby
 target cells by secreting
molecules of a local regulator
(a growth factor, for
example):
b. Synaptic Signaling: A nerve
cell releases neurotransmitter
molecules into a synapse,
stimulating the target cell,
such as a muscle or another
nerve cell.
The Three Stages of Cell Signaling
● REMEMBER: Synaptic signaling is
similar to paracrine signaling but
there is a special structure called the
synapse between the cell originating
and the cell receiving the signal.
Synaptic signaling only occurs
between cells with the synapse; for
example between a neuron and the
muscle that is controlled by neural
activity.
● Long-distance signaling involves
molecules that travel long distances
in the body. Both animals and plants
use molecules called hormones for
long-distance signaling. In hormonal
signaling in animals, also known as
endocrine signaling, specialized
cells release hormones, which travel
via the circulatory system to other
parts of the body, where they reach
target cells that can recognize and
respond to them. Plant hormones
(often called plant growth
regulators) sometimes travel in plant
vessels (tubes) but more often reach
their targets by moving through cells
or by diffusing through the air as a
gas.
● The ability of a cell to respond is
determined by whether it has a
specific receptor molecule that can
bind to the signaling molecule.
● Earl W. Sutherland led how the
animal hormone epinephrine (also
called adrenaline) triggers the
“fight-or-flight” response in animals
by stimulating the breakdown of the
storage polysaccharide glycogen
within liver cells and skeletal muscle
cells.
● Thus, one effect of epinephrine is the
mobilization of fuel reserves, which
can be used by the animal to either
defend itself (fight) or escape
whatever elicited a scare (flight).
● Epinephrine does not interact
directly with the enzyme responsible
for glycogen breakdown; an
intermediate step or series of steps
must be occurring in the cell. And an
intact, membrane-bound cell must
be present for transmission of the
signal to take place.
● There are three stages of signal
transduction: reception,
transduction, and response.
● Reception is the target cell’s
detection of a signaling molecule
coming from outside the cell.
● Transduction is the binding of the
signaling molecule that changes the
receptor protein in some way,
initiating the process of
transduction. The transduction stage
converts the signal to a form that
can bring about a specific cellular
response.
● Relay molecules are the molecules
in the signal transduction pathway.
● Response is the third stage of cell
signaling in which the transduced
signal finally triggers a specific
cellular response.
● The cell-signaling process helps
ensure that crucial activities occur in
the right cells, at the right time, and
in proper coordination with the
activities of other cells of the
organism.
Reception
● Reception of the signal depends on
the receiver.
● A receptor protein on or in the target
cell allows the cell to “hear” the
signal and respond to it. The
signaling molecule is complementary
in shape to a specific site on the
receptor and attaches there, like a
hand in a glove.
● The signaling molecule acts as a
ligand, the term for a molecule that
specifically binds to another (often
larger) molecule.
● Ligand binding generally causes a
receptor protein to undergo a
change in shape.
● For other kinds of receptors, the
immediate effect of ligand binding is
to cause the aggregation of two or
more receptor proteins, which leads
to further molecular events inside
the cell.
Receptors in the Plasma Membrane
● The largest family of human cell
surface receptors is the G
protein-coupled receptors (GPCRs).
● We can see how cell-surface
transmembrane receptors work by
looking at three major types: G
protein-coupled receptors (GPCRs),
receptor tyrosine kinases, and ion
channel receptors.
● A G protein-coupled receptor
(GPCR) is a cell-surface
transmembrane receptor that works
with the help of a G protein, a
protein that binds the energy-rich
molecule GTP.
● GPCR-based signaling systems are
extremely widespread and diverse in
their functions, including roles in
embryonic development and sensory
reception.
● The bacteria that cause cholera,
pertussis (whooping cough), and
botulism, among others, make their
victims ill by producing toxins that
interfere with G protein function.
● (1) Attached but able to move along
the cytoplasmic side of the
membrane, a G protein functions as
a molecular switch that is either on
or off, depending on whether GDP or
GTP is attached —hence the term G
protein. (GTP, or guanosine
triphosphate, is similar to ATP.) When
GDP is bound to the G protein, as
shown above, the G protein is
inactive. The receptor and G protein
work together with another protein,
usually an enzyme. (2) When the
appropriate signaling molecule binds
to the extracellular side of the
receptor, the receptor is activated
and changes shape. Its cytoplasmic
side then binds an inactive G protein,
causing a GTP to displace the GDP.
 This activates the G protein. (3)
When the appropriate signaling
molecule binds to the extracellular
side of the receptor, the receptor is
activated and changes shape. Its
cytoplasmic side then binds an
inactive G protein, causing a GTP to
displace the GDP. This activates the
G protein. (4) The changes in the
enzyme and G protein are only
temporary because the G protein
also functions as a GTPase
enzyme—in other words, it then
hydrolyzes its bound GTP to GDP
and . Now inactive again, the G
protein leaves the enzyme, which
returns to its original state. The G
protein is now available for reuse.
The GTPase function of the G protein
allows the pathway to shut down
rapidly when the signaling molecule
is no longer present.
● SUMMARY: (1) Ligand binds to GPCR
(2) GPCR undergoes conformational
change (3) Alpha subunit exchanges
GDP for GTP (4) Alpha subunit
dissociates and regulates target
proteins (5) Target protein relays
signal via 2nd messengers (6) GTP
hydrolyzed to GDP.
● Receptor tyrosine kinases (RTKs)
belong to a major class of plasma
membrane receptors characterized
by having enzymatic activity. An
RTK is a protein kinase—an enzyme
that catalyzes the transfer of
phosphate groups from ATP to
another protein.
● RTKs are membrane receptors that
attach phosphates to tyrosines.
● One RTK may activate ten or more
different transduction pathways and
cellular responses.
● The ability of a single ligand-binding
event to trigger so many pathways is
a key difference between RTKs and
GPCRs, which generally activate a
single transduction pathway.
● SUMMARY: (1) Ligands bind to two
monomer RTKs (2) The monomers of
RTKs bind to form a dimer in a
process called dimerization (3) This
dimerization activates the tyrosine
kinase region adding a phosphate
from ATP molecules to a tyrosine
part (4) Relay proteins bind to each
phosphorylated tyrosine resulting to
structural change that can trigger
numerous signal transduction
pathways that will lead to a cellular
response.
● A ligand-gated ion channel is a
type of membrane channel receptor
containing a region that can act as a
“gate,” opening or closing the
channel when the receptor changes
shape.
● Ligand-gated ion channels are very
important in the nervous system.
● The neurotransmitter molecules
released at a synapse between two
nerve cells bind as ligands to ion
channels on the receiving cell,
causing the channels to open. Ions
flow in (or, in some cases, out),
triggering an electrical signal that
propagates down the length of the
receiving cell.
● Some ion channels are present on
membranes of organelles, such as
the ER.
● SUMMARY: (1) Ligand binds to a
ligand-gated ion channel (2) Ion
channels undergo a change in shape
causing ions to rush into the cell
changing the concentration (3)
Ligand dispatches from the channel,
closing it.
Intracellular Receptors
● Intracellular receptor proteins are
found in either the cytoplasm or
nucleus of target cells. To reach such
a receptor, a signaling molecule
passes through the target cell’s
plasma membrane.
● A number of important signaling
molecules can do this because they
are either hydrophobic enough or
 small enough to cross the
hydrophobic interior of the
membrane.
● Once a hormone has entered a cell,
its binding to an intracellular
receptor 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.
● With aldosterone attached, the
active form of the receptor protein
then enters the nucleus and turns on
specific genes that control water
and sodium flow in kidney cells,
ultimately affecting blood volume.
● Special proteins called transcription
factors control which genes are
turned on—that is, which genes are
transcribed into mRNA— in a
particular cell at a particular time.
Transduction
● The transduction stage of cell
signaling is usually a multistep
pathway involving many
molecules.
● One benefit of multiple steps is the
possibility of greatly amplifying a
signal.
● Multistep pathways provide more
opportunities for coordination and
control than do simpler systems.
● The molecules that relay a signal
from receptor to response are called
relay molecules, are often proteins.
● The phosphorylation and
dephosphorylation of proteins is a
widespread cellular mechanism for
regulating protein activity. An
enzyme that transfers phosphate
groups from ATP to a protein is
generally known as a protein
kinase.
● Many of the relay molecules in signal
transduction pathways are protein
kinases, and they often act on other
protein kinases in the pathway.
● In a phosphorylation cascade, a
series of different proteins in a
pathway are phosphorylated in turn,
each protein adding a phosphate
group to the next one in line. Here,
phosphorylation activates each
protein, and dephosphorylation
returns it to its inactive form. The
active and inactive forms of each
protein are represented by different
shapes to remind you that activation
is usually associated with a change
in molecular shape.
● About 2% of our own genes are
thought to code for protein kinases,
a significant percentage.
● Protein phosphatases are enzymes
that can rapidly remove phosphate
groups from proteins, a process
 called dephosphorylation.
● Phosphatases provide
mechanism for turning off the signal
transduction pathway when the
initial signal is no longer present.
● The
phosphorylation-dephosphorylatio
n system acts as a molecular switch
in the cell, turning activities on or
off, or up or down, as required.
● The activity of a protein regulated
by phosphorylation depends on the
balance in the cell between active
kinase molecules and active
phosphatase molecules.
● Many signaling pathways also
involve small, nonprotein,
water-soluble molecules or ions
called second messengers.
● The pathway’s “first messenger” is
considered to be the extracellular
signaling molecule—the ligand—that
binds to the membrane receptor
● Because second messengers are
small and also water-soluble, they
can readily spread throughout the
cell by diffusion.
● The two most widely used second
messengers are cyclic AMP and
calcium ions, Ca2+ .
● The binding of epinephrine to the
plasma membrane of a liver cell
elevates the cytosolic concentration
of cyclic AMP (cAMP; cyclic
adenosine monophosphate).
● Adenylyl cyclase (also known as
adenylate cyclase), converts ATP to
cAMP in response to an extracellular
signal.
● Phosphodiesterase converts cAMP
to AMP.
● The immediate effect of an elevation
in cAMP levels is usually the
activation of a serine/threonine
kinase called protein kinase A.
the
● Our understanding of signaling
pathways involving cyclic AMP or
related messengers has allowed us
to develop treatments for certain
conditions in humans.
● Cyclic GMP (cGMP) is produced by a
muscle cell in response to the gas
nitric oxide (NO) after it is released
by a neighboring cell. Under the
trade name Viagra, this compound is
now widely used as a treatment for
erectile dysfunction in human males.
● Calcium is even more widely used
than cAMP as a second messenger.
Increasing the cytosolic
concentration of Ca2+ causes many
responses in animal cells, including
muscle cell contraction, exocytosis of
molecules (secretion), and cell
division.
● Cells use Ca2+ as a second
messenger in pathways triggered by
both G protein-coupled receptors
and receptor tyrosine kinases.
● Although cells always contain some
Ca2+ , this ion can function as a
second messenger because its
concentration in the cytosol is
normally much lower than the
concentration outside the cell.
● Calcium ions are actively
transported out of the cell and are
actively imported from the cytosol
into the endoplasmic reticulum (and,
under some conditions, into
mitochondria and chloroplasts) by
 various protein pumps. As a result,
the calcium concentration in the
ER is usually much higher than
that in the cytosol.
● In response to a signal relayed by a
signal transduction pathway, the
cytosolic calcium level may rise,
usually by a mechanism that
releases Ca2+ from the cell’s ER. The
pathways leading to calcium release
involve two other second
messengers, inositol trisphosphate
(IP3) and diacylglycerol (DAG).
These two messengers are produced
by cleavage of a certain kind of
phospholipid in the plasma
membrane.
Response
● The response at the end of the
pathway may occur in the nucleus of
the cell or in the cytoplasm.
● Many signaling pathways ultimately
regulate protein synthesis, usually by
turning specific genes on or off in
the nucleus.
● The transcription factor might
regulate a gene by turning it off.
● Sometimes a signaling pathway may
regulate the activity of proteins
rather than causing their synthesis
by activating gene expression.
● A signal may cause the opening or
closing of an ion channel in the
plasma membrane or a change in
the activity of a metabolic enzyme.
● Signal receptors, relay molecules,
and second messengers participate
in a variety of pathways, leading to
both nuclear and cytoplasmic
responses, including cell division.
● FOUR ASPECTS OF REGULATION
OF RESPONSE: (1) Amplification, (2)
Specificity & Coordination, (3)
Scaffolding Proteins, (4) Termination
● Signaling pathways generally
amplify the cell’s response to a
single signaling event.
● The many steps in a multistep
pathway provide control points at
which the cell’s response can be
further regulated, contributing to the
specificity of the response and
allowing coordination with other
signaling pathways.
● The overall efficiency of the
response is enhanced by the
presence of proteins known as
scaffolding proteins.
● Signal Amplification occurs when
elaborate enzyme cascades amplify
the cell’s response to a signal.
● The number of activated products
can be much greater than in the
preceding step.
 responses to information coming in
from different sources in the body.

● A small number of epinephrine

molecules binding to receptors on
the surface of a liver cell or muscle
cell can lead to the release of
hundreds of millions of glucose
molecules from glycogen.
● Specificity & Coordination:
different kinds of cells turn on
different sets of genes, different ● Scaffolding proteins are large relay
kinds of cells have different proteins to which several other relay
collections of proteins. The response proteins are simultaneously
of a cell to a signal depends on its attached.
particular collection of signal ● The function of scaffolding proteins
receptor proteins, relay proteins, and is to bring together two or more
proteins needed to carry out the proteins in a relatively stable
response. configuration.
● Two cells that respond differently to
the same signal differ in one or more
proteins that respond to the signal.
● Branching of pathways and
“cross-talk” (interaction) between
pathways are important in
regulating and coordinating a cell’s
● If a signaling pathway component
becomes locked into one state,
whether active or inactive,
consequences for the organism can
be serious.
● The binding of signaling molecules
to receptors is reversible.
● 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.
Apoptosis
● Cells that are infected, are
damaged, or have reached the end
of their functional lifespan often
undergo “programmed cell death”
● The best-understood type of this
controlled cell suicide is apoptosis
(from the Greek, meaning “falling
off,” and used in a classic Greek
poem to refer to leaves falling from
a tree).
● The cell shrinks and becomes lobed
(a change called “blebbing”) and
the cell’s parts are packaged up in
vesicles that are engulfed and
digested by specialized scavenger
cells, leaving no trace.
● Apoptosis protects neighboring cells
from damage that they would
otherwise suffer if a dying cell
merely leaked out all its contents,
including its many digestive
enzymes.
● The signal that triggers apoptosis
can come from either outside or
inside the cell.
● Outside the cell, signaling molecules
released from other cells can initiate
a signal transduction pathway that
activates the genes and proteins
responsible for carrying out cell
death. Within a cell whose DNA has
been irretrievably damaged, a series
of protein-protein interactions can
pass along a signal that similarly
triggers cell death.
● In worms and other species,
apoptosis is triggered by signals that
activate a cascade of “suicide”
proteins in the cells destined to die.
● The proteins are called Ced-3 and
Ced-4, respectively. These and most
other proteins involved in apoptosis
are continually present in cells, but in
inactive form; thus, regulation in this
case occurs at the level of protein
activity rather than through gene
activity and protein synthesis.
● Ced-9 (the product of the ced-9
gene), serves as a master regulator
of apoptosis, acting as a brake in the
absence of a signal promoting
apoptosis .
● One major pathway involves certain
mitochondrial proteins that are
triggered to form molecular pores in
the mitochondrial outer membrane,
causing it to leak and release other
proteins that promote apoptosis.
● Cytochrome c, which functions in
mitochondrial electron transport in
healthy cells but acts as a cell death
factor when released from
mitochondria.
● Two other types of alarm signals
that can lead to apoptosis originate
from inside the cell rather than from
a cell-surface receptor. One signal
comes from the nucleus, generated
when the DNA has suffered
irreparable damage, and a second
comes from the endoplasmic
reticulum when excessive protein
 misfolding occurs. Mammalian cells
make life-or-death “decisions” by
somehow integrating the death
signals and life signals they receive
from these external and internal
sources
● In vertebrates, apoptosis is essential
for normal development of the
nervous system, for normal
operation of the immune system,
and for normal morphogenesis of
hands and feet in humans and paws
in other mammals.
● The failure of appropriate apoptosis
can result in webbed fingers and
toes.
● In Alzheimer’s disease, an
accumulation of aggregated
proteins in neuronal cells activates
an enzyme that triggers apoptosis,
resulting in the loss of brain function
seen in these patients.
● Furthermore, 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.