Cell Communication
For cells to function in a biological system, they must communicate with other
cells and respond to their external environment.
Enduring understanding :
Cells communicate by generating, transmitting and receiving
chemical signals.
Essential knowledge:
1. Cell communication processes share common features
that reflect a shared evolutionary history.
2. Cells communicate with each other through direct contact
with other cells or from a distance via chemical signaling.
3. Signal transduction pathways link signal reception with
cellular response.
4. Changes in signal transduction pathways can alter cellular
response.
5. Organisms respond to changes in their external
environments.
Chemical Signals….
• Can direct complex processes, ranging from cell
and organ differentiation to whole organism
physiological responses and behaviors.
• Can allow cells to communicate without physical
contact.
• The distance between the signal generating
cell(s) and the responding cell can be small
or large.
Methods of cell communication
Three general methods of cell communication:
1.Diffusible chemical signals (messengers)
that travel through the organism from one
location to another (Close or long distances)
2.Physical contact between adjacent cell
plasma membranes
3.Direct cytoplasmic contact via gap junctions
CELL COMMUNICATION
Part 1:
An Overview of Cell Signaling
1.Cell signaling evolved early in the
history of life
2.Communicating cells may be close
together or far apart
3.The three stages of cell signaling are
reception, transduction, and response
Introduction
• Cell-to-cell communication is absolutely essential
for multicellular organisms.
– coordinate the activities within individual cells that
support the function of the organism as a whole.
– Use of pheromones to trigger reproduction and
developmental pathways
• Important for many unicellular organisms.
•
•
•
•
finding a mate
population density (quorum sensing)
Response to external signals by bacteria that influences cell
allowed some organisms to evolve without having a nervous
system.
1-Cell signaling evolved
early in the history of life
One topic of cell
“conversation” is “mating”.
– Ex: The yeast Saccharomyces
cerevisiae, the yeast of bread,
wine, and beer, identifies its
mates by chemical signaling.
– There are two sexes, a and
alpha, each of which secretes a
specific signaling molecule, a
factor and alpha factor
respectively.
– These factors each bind to
receptor proteins on the other
mating type.
Cell signaling has remained important in the
microbial world.
– Myxobacteria, soil-dwelling bacteria, use chemical
signals to communicate nutrient availability.
– When food is scarce, cells secrete a signal to other cells
leading them to aggregate and form thick-walled
spores.
2-Communicating cells
may be close together
(LOCAL) or far apart
Local signaling
Target cell
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling. A secreting cell acts
on nearby target cells by discharging
molecules of a local regulator (a growth
factor, for example) into the extracellular
fluid.
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Target cell is stimulated
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Example of Localized signaling
Local signaling
c. In synaptic
signaling, a nerve
cell produces the
neurotransmitter
that diffuses to a
single cell that is
almost touching
the sender.
–An electrical signal passing along the nerve cell
triggers secretion of the neurotransmitter into
the synapse.
Local signaling
d. Contact dependent
Touching
*Plasmodesmata
•Narrow channels between
plant cells
•A narrow tube of
Endoplasmic reticulum.
•Material exchange
*Gap Junctions
•Narrow tunnels between
animal cells that consist of
proteins called connexons.
•Allows the movement of
ions and small molecules
from cell to cell.
Local signaling
d. Contact dependent
– Signaling
substances
dissolved in the
cytosol pass
freely between
adjacent cells.
Touching
Clip; Start at 5:30
Long-Distance Signaling
• Endocrine (hormone) signaling
– Specialized cells release hormone
molecules, which travel (usually by
diffusion through cells or through the
circulatory system) to target cells
elsewhere in the organism
Hormone Control Clip
Long-Distance Signaling
• Plants also use
hormones to signal at
long distances.
-In plants, hormones
may travel in vessels,
but more often travel
from cell to cell (auxin)
or by diffusion in air
(Ethylene).
-Ethylene gas
in fruit ripening
3. The three stages of cell signaling:
reception, transduction, & response
McGraw-Hill
Dehydration
Response
Example Clip
EK: Signal
transduction
pathways link
signal
reception with
cellular
response.
The three stages of cell signaling
CELL COMMUNICATION
Part 2: Signal Reception and the Initiation of Transduction
Step #1: In reception, a chemical signal binds to
a cellular protein, typically at the cell’s surface.
A signal molecule (ligand), binds to a receptor
protein, causing the protein to change shape
Step 1. A signal molecule binds to a receptor
protein causing the protein to change shape
• Receptor protein recognizes the signal molecule
(ligand).
– Recognition: receptor on target cell is
complementary in shape.
– The ligand attaches to the receptor
protein, the receptor typically undergoes a
change in shape.
1. This may activate the receptor so that
it can interact w/other molecules inside the cell.
2. Can lead to the aggregation of
receptors.
**Signal molecule does not enter
cell.***
Most signal receptors are plasma
membrane proteins
 Most signal molecules are water-soluble and too
large to pass through the plasma membrane.
 Three major types of receptors:
1. G-protein-linked receptors
–
short for guanine nucleotide binding proteins
2. Tyrosine-kinase receptors
3. Ion-channel receptors
• PROJECTS START HERE
G protein-linked receptors
1. G-protein-linked receptors consists of a
receptor protein associated with a Gprotein on the cytoplasmic side.
– The receptor consists of seven alpha helices spanning the
membrane.
– Effective signal
molecules include
yeast mating factors,
epinephrine, other
hormones, and
neurotransmitters.
GGprotein-coupled
protein-linked receptors
receptors
 An example of a G protein-linked receptor is the
epinephrine receptor.
 Epinephrine stimulates glycogen breakdown
 G-protein-linked receptors and G-proteins mediate a
host of critical metabolic and developmental processes
(e.g., blood vessel growth and development).
G protein-linked receptors
•Uses the exchange of Guanosine diphosphate (GDP) for
Guanosine triphosphate (GTP) as a molecular "switch" to
allow or inhibit biochemical reactions inside the cell
G proteincoupled
receptors

Large family all
with 7
membranespanning regions
Receptor
Receptor
Ion
channel



G protein
Second
messenger
Effector
enzyme
Precursor
coupled to G protein,
and G protein stimulates effector
(enzyme that promotes formation of intracellular
“second messenger”)
Guanosine
triphosphate
The G-protein system cycles between on & off.
1. When a G-protein-linked receptor is activated by
binding with an extracellular signal molecule, the
receptor binds to an inactive G protein in
membrane.
2. This leads the G protein to substitute GTP for
GDP.
3. The G protein then binds with another membrane
protein, often
an enzyme,
altering its
activity and
leading to
a cellular
response.
The whole system can be shut down quickly when
the extracellular signal molecule is no longer
present.
G-Protein receptors:
• Diseases such as diabetes and certain
forms of pituitary cancer, among many
others, are thought to have some root in
the malfunction of G proteins
• G-protein receptor systems are extremely
widespread and diverse in their functions.
– They play an important role during embryonic
development and sensory systems.
Ion-Channel receptors
Ligand binding changes confirmation of the receptor so
that specific ions can flow through it
Ion movement alters the electric potential across the
plasma membrane
found in high numbers on neuron plasma membranes
ligand-gated channels for sodium and potassium
Also found on the plasma membrane of muscle cells
binding of acetylcholine results in ion movement and eventual
contraction of muscle
Extracellular side
Closed
Open
Binding
Cytoplasmic side
3.Ligand-gated ion channels:
protein pores that open or
close in response to a
chemical signal.
– This allows or blocks ion
flow, such as Na+ or Ca2+.
– Binding by a ligand to the
extracellular side changes
the protein’s shape and
opens the channel.
– Ion flow changes the
concentration inside the
cell.
– When the ligand
dissociates, the channel
closes.
• Ligand-gated ion channels are
very important in the nervous
system.
– EX: binding of a neurotransmitter
to a neuron, allowing the inward flow
of Na2+ that leads to the
depolarization of the neuron and the
propagation of a nervous impulse to
adjacent cells.
This colored scanning electron
micrograph shows the synapses, or
connections, between two nerve
fibers (in purple) and a nerve cell
(yellow). The picture is magnified
10,000 times.
Way Cool Alert!
•Normally, the enzyme
acetylcholinesterase converts
acetylcholine into the inactive
metabolites choline and acetate.
•The devastating effects of
nerve agents (Sarin gas for
example) are due to their
inhibition of this enzyme,
resulting in continuous
stimulation of the muscles,
glands and central nervous
system.
•Botulinus toxin is produced by the anerobic bacillus Clostridium botulinum,
which may be found in improperly canned food, and is one of the most potent
toxins known.
•This toxin (the agent responsible for botulism) blocks the release of vesicles.
This, of course, leads to muscle paralysis and, if the diaphragm becomes
affected, can be fatal.
Tyrosine Kinase-linked receptors
Activation:
**Aggregation then phosphorylation
 Ligand binding results in the formation of a receptor dimer (2
receptors)
 The dimer then activates a class of protein called tyrosine
kinases
 This activation results in the phosphorylation of downstream
targets by these tyrosine kinases (stick phosphate groups onto
tyrosines within the target protein)
Protein Kinases= general name for an enzyme that transfers PO4- groups from ATP
to a protein
An individual tyrosine-kinase
receptor consists of several parts:
– an
extracellular
signal-binding
sites
– a single alpha
helix
spanning the
membrane,
and
– an
intracellular
tail with
several
tyrosines.
• When ligands bind
to two receptor
polypeptides, the
polypeptides
aggregate,
forming a dimer.
• This activates
the tyrosinekinase section of
both.
• These add
phosphates to the
tyrosine tails of
the other
polypeptide.
• The fully-activated receptor proteins
activate a variety of specific relay proteins
that bind to specific phosphorylated
tyrosine molecules.
– One tyrosine-kinase receptor dimer may
activate ten or more different intracellular
proteins simultaneously.
• These activated relay
proteins trigger many
different transduction
pathways and
responses.
The tyrosine-kinase receptor system is especially
effective when the cell needs to regulate and
coordinate a variety of activities and trigger
several signal pathways at once.
– Extracellular growth factors often bind to tyrosinekinase receptors.
Signal-binding sitea
Signal
molecule
Signal
molecule
Helix in the
Membrane
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Dimer
Activated
relay proteins
P Tyr
Tyr P
Tyr P
P Tyr
Tyr P
Tyr P
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
6
Activated tyrosinekinase regions
(unphosphorylated
dimer)
ATP
6 ADP
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Insulin
(Click)
Polypeptide
hormone that
regulates
carbohydrate
metabolism.
• PROJECTS END HERE
Step #1 Continued:
Communication through
diffusion- intracellular receptors
• Some signal receptors are
dissolved in the cytosol or
nucleus of target cells.
• The ligands pass through
the plasma membrane.
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
• Include the hydrophobic
steroid and thyroid
hormones of animals.
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Action of Lipid-Soluble Hormones (steps)
1. Hormone diffuses
through phospholipid
bilayer & into cell
2. (Step #1) Binds to an
intercellular
receptor turning
on/off specific
genes
3. (Step #3-response) Causing
the synthesis of new
proteins
4. New proteins alters
cell’s activity
• Testosterone, like EXAMPLE
other hormones, travels
through the blood and
enters cells throughout
the body.
• In the cytosol, they
bind and activate
receptor proteins.
• These activated
proteins enter the
nucleus and turn on
genes that control male
sex characteristics.
• These activated
proteins act as
transcription factors.
– Transcription factors
control which genes are
turned on which genes
get transcribed into
messenger RNA
(mRNA).
• The mRNA molecules
leave the nucleus and
carry information that
directs the synthesis
(translation) of specific
proteins at the
ribosome.
Part 3:
Signal-Transduction Pathways
Step #2. In transduction, binding leads to a change in the
receptor that triggers a series of changes along a signaltransduction pathway.
 Pathways relay signals from receptors to
cellular responses-Usually a multi-step
pathway
 Amplification (small number of signal
molecules can produce a large cellular
response)
 Protein phosphorylation, a common mode of
regulation in cells, is a major mechanism of
signal transduction
 Certain small molecules and ions are key
components of signaling pathways (second
messengers-cAMP, Ca2+,IP3, GMP )
Insulin Signaling Clip
Mr. Anderson: Signal Transduction Pathways
Pathways relay signals from
receptors to cellular responses
• Pathway acts like
falling dominoes.
– The signal-activated receptor
activates another protein, which
activates another and so on, until
the protein that produces the final
cellular response is activated.
• The original signal
molecule is not passed
along the pathway and
may not even enter the
cell.
– Its information is passed on.
Protein phosphorylation is a major
mechanism of signal transduction
• The phosphorylation of
proteins by a specific enzyme
(a protein kinase) is a
widespread cellular mechanism
for regulating protein
activity.
– Most protein kinases act on other
substrate proteins, unlike the
tyrosine kinases that act on
themselves.
phosphorylation
dephosphorylation
**Phosphorylation is the addition of a phosphate (PO4) group to a
protein or a small molecule
**Many enzymes and receptors are switched "on" or "off" by
phosphorylation and dephosphorylation.
• Phosphorylation of a
protein typically converts it
from an inactive form to an
active form.
ON
protein kinase
phosphorylation
– The reverse (inactivation) is
possible too for some proteins.
• A single cell may have
hundreds of different protein
kinases, each specific for a
different substrate protein.
– Fully 1% of our genes may
code for protein kinases.
• Abnormal activity of protein
kinases can cause abnormal cell
growth and contribute to the
development of cancer.
dephosphorylation
protein phosphatases
OFF
• Turning off a signaltransduction pathway protein phosphatases.
ON
phosphorylation
– Rapidly remove
phosphate groups from
proteins.
• When an extracellular
signal molecule is
absent, active
phosphatase molecules
predominate, and the
signaling pathway and
cellular response are
shut down.
dephosphorylation
OFF
Certain signal molecules and ions are key
components of signaling pathways
(second messengers- cAMP, Ca2+,IP3, GMP )
• Many signaling pathways
involve small, nonprotein,
water-soluble molecules
or ions, called second
messengers.
– These molecules
rapidly diffuse
throughout the cell.
– Two of the most
important 2nd
messangers are cAMP
and Ca2+.
– Inositol triphosphate
(IP3) & GMP are others
•Binding by epinephrine leads to increases
the concentration of cyclic AMP or cAMP.
– This occurs because
the receptor activates
adenylyl cyclase,
which converts ATP to
cAMP.
– cAMP is short-lived as
phosphodiesterase
converts it to AMP.
McGraw-Hill Animation
Epinephrine stimulates glycogen breakdown
in
cAMP
cAMP:
-Main purpose:
activation of
protein kinases.
-also used to
regulate the passage
of Ca2+ through ion
channels.
Receptor
Gs
cAM P
cAMP
Adenylyl
cyclase
AT P
Activate protein kinase
(phosphorylate protein)
(dephosphorylate b
phosphoprotein
phosphatase)
Biological
response
cAMP is synthesised from ATP by adenylyl cyclase.
Adenylate cyclase is located at the cell membranes. It is
activated by the hormones glucagon (does the opposite of insulin)
and adrenaline and by G protein
cAMP controls many biological processes, including glycogen
decomposition into glucose (glycogenolysis), and lipolysis
In response to a signal, a cell may
regulate activities in the cytoplasm or
transcription in the nucleus
• Ultimately, a signal-transduction pathway
leads to the regulation of one or more cellular
activities.
– This may be a change in an ion channel or a
change in cell metabolism.
– EX:, epinephrine activates enzymes that catalyze
the breakdown of glycogen.
Secondary messengers clip- click
• Hormones and other signals can
trigger the formation of cAMP.
cAMP
– Binding by the signal to a receptor activates a
G protein that activates adenylyl cyclase in
the plasma membrane.
–The cAMP from the
adenylyl cyclase
diffuses through the
cell and activates a
serine/threonine
kinase, called protein
kinase A
which phosphorylates
other proteins.
• Certain microbes cause
disease by disrupting the Gprotein signaling pathways.
cAMP
– The cholera bacterium, colonizes
the small intestine and produces a
toxin that modifies a G protein that
regulates salt and water secretion.
– The modified G protein is stuck in
its active form, continuously
stimulating productions of cAMP.
– This causes the intestinal cells to
secrete large amounts of water and
salts into the intestines, leading to
profuse diarrhea and death if
untreated.
The toxin acts as an enzyme
that changes the G protein so
that it can no longer switch
itself off
•Ca Many signal molecules in animals induce responses in
their target cells via signal-transduction pathways that
increase the cytosolic concentration of Ca2+.
2+
– In animal cells, increases in Ca2+ may cause contraction of muscle
cells, secretion of some substances, and cell division.
– In plant cells, increases in Ca2+ trigger responses for coping with
environmental stress, including drought.
• Cells use Ca2+ as a second messenger in both G-protein
pathways and tyrosine-kinase pathways.
Ca2+.
Other secondary messengers:
inositol triphosphate (IP3)- -stimulates the release of calcium ions from the
smooth endoplasmic reticulum
1
2
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
3
DAG functions as
a second messenger
in other pathways.
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
Signal molecule
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
PIP2
Phospholipase C
IP3
(second messenger)
Skip…Should beIPin-gated
student projects
3
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
Ca2+
(second
messenger)
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
5
Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
Various
proteins
activated
Cellular
response
6 The calcium ions
activate the next
protein in one or more
signaling pathways.
CELL COMMUNICATION
Part 4:
Cellular Responses
(step#3)
to Signals
• In response to a signal, a cell may
regulate activities in the cytoplasm
or transcription in the nucleus
• Elaborate pathways amplify and
specify the cell’s response to signals
• The stimulation of glycogen breakdown
by epinephrine
involves a G-proteinlinked receptor,
a G Protein
adenylyl cyclase
and cAMP, and
Notice: The cascading and
several protein
amplifying effect…
kinases before
glycogen
phosphorylase
is activated.
• Other signaling
pathways do not
regulate the
activity of enzymes
but the synthesis of
enzymes or other
proteins.
• Activated receptors
may act as
transcription
factors that turn
specific genes on or
off in the nucleus.
Pathways amplify and specify the cell’s response to signals
• Pathways with multiple steps have 2 benefits.
1. They amplify the response to a signal.
• At each catalytic step in a cascade, the number of
activated products is much greater than in the
preceding step.
– In the epinephrine-triggered pathway, binding by a
small number of epinephrine molecules can lead to
the release of hundreds of millions of glucose
molecules.
2. They contribute to the specificity of the
response.
• Various types of cells may receive the
same signal but produce very different
click
responses.
– For example, epinephrine triggers liver or
striated muscle cells to break down glycogen,
but cardiac muscle cells are stimulated to
contract, leading to a rapid heartbeat.
• These differences result from a basic
observation:
– Different kinds of cells have different collections
of proteins.
• STRUCTURE AND FUNCTION.
• 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.
• As important as activating mechanisms are, we
must say something about inactivating mechanisms.
1. For a cell to remain alert and capable of responding to
incoming signals, each molecular change in its signaling
pathways must last only a short time.
• If signaling pathway components become locked into one state,
the proper function of the cell can be disrupted.
2. Binding of signal molecules to receptors must be
reversible, allowing the receptors to return to their
inactive state when the signal is released.
• Similarly, activated signals (cAMP and phosphorylated
proteins) must be inactivated by appropriate enzymes to
prepare the cell for a fresh signal.
Extracellular Signaling Review
1.
2.
3.
4.
5.
6.
Signaling molecules are released by signaling cells
The signal is called the ligand
The ligand binds to its specific receptor on a target
cell
This ligand-receptor interaction induces a
conformational or shape-change in the receptor
Produces a specific response - called the cellular
response
Can include a vast array of compounds
e.g. small amino acid derivatives, small peptides, proteins
Cell-to-cell communication by extracellular
signaling usually involves six steps
•
•
•
•
(1) synthesis of the signaling molecule by the signaling cell
(2) release of the signaling molecule by the signaling cell
(3) transport of the signal to the target cell
(4) detection of the signal by a specific receptor protein –
receptor-ligand specificity
• (5) a change in cellular metabolism, function, or
development = cellular response
– triggered by the receptor-ligand complex – specific to the ligandreceptor complex
• (6) removal of the signal, which usually terminates the
cellular response – degredation of ligand