Chapter 11: Cell Communication
I.
Why do cells communicate?
A. Regulation – cells need to control cellular processes
Ex:
B. Environmental Stimuli – cells need to be able to respond to
signals from their environment
Ex:
II. Stages of cell signaling:
A. Reception –
signaling molecule binds to a
receptor protein in the membrane
B. Transduction –
passing on the signal
(can occur in one step, but
is usually a sequence of
changes in a series of “relay
molecules”) “transduction
pathway”
C. Response cellular changes
because of the
signal (catalysis by an enzyme,
rearrangement of the cytoskeleton,
activation of a specific gene.)
III. More Detail
A. Reception
1. Signal will only be “heard” by a specific cell.
2. Types of signaling:
a. Direct Contact
cell junctions; signaling substances dissolved in
cytosol are shared (ex: plasmodesmata, gap junctions)
membrane bound cell-surface molecules that touch
another cell (cell recognition, embryonic development, immuneresponse)
b. Local signaling – influence cells in the vicinity
Paracrine Signaling
Synaptic Signaling
c. Long-distance Signaling -- Use Hormones(Endrocrine
signaling)
Local and Long Distance Signaling Examples
Growth Factor
Cell secretes molecule (“local
regulator”) into extracellular
fluid to influence neighboring
cells
Nervous System
More specialized than
paracrine. Nerve cell releases a
neurotransmitter that
stimulates the target cell.
Hormones
Specialized cells release
hormones into circulatory system
that carries them to target cells in
other parts of the body.
AKA – “endocrine signaling”
3. Signal molecules
a. often water soluble
b. usually too large to travel through membranes
c. behave as “ligands” – smaller molecule binding to a
larger one.
4. Receptor molecules
a. Usually a protein…most are located within the cell
membrane (G-protein coupled, tyrosine-kinase, ion channels)
b. some are located inside the cell…in the cytoplasm or
nucleus of target cell (usually acts as a transcription
factor to turn on specific genes). (see slide 15 for more detail)
c. Changes shape when bound to signal molecule
d. Transmits information from the exterior to the interior
of the cell.
e. Types of receptor molecules: page 211, 212, 213
G-protein coupled receptor
Very widespread and diverse in functions.
Ex - vision, smell, blood vessel development.
Many diseases work by affecting g-protein linked receptors.
Ex - whooping cough, botulism, cholera, some cancers
(toxins interfere with G-protein function)
Up to 60% of all medicines exert their effects through G-protein linked
receptors.
Tyrosine-kinase
Ion channels
Intracellular Receptors
G-Protein Coupled Receptor (page 211)
Works with the help of a G-protein (protein that binds to GTP)
The receptor has a variety of binding sites for different signal
molecules and for different G-proteins. There are different “Gproteins” out there.
All G-protein coupled receptors have a similar structure.
(7 alpha helices spanning the membrane)
The “loops” are binding sites for signals and G-proteins
Examples:
yeast mating factors
epinephrine
neurotransmitters
How the G-Protein Coupled
Receptor works (page 211)
Works with “G-protein”, an intracellular
protein that binds with GDP (G-protein is
inactive) or GTP (G-protein is active).
When signal binds to receptor, the
receptor changes shape…this allows it to
bind to an inactive G-protein that is on the
cytoplasmic side of the membrane. GTP
displaces GDP to activate the G-protein.
Now active (GTP is bound to it), the Gprotein binds to an enzyme and alters the
enzymes shape and activity. It triggers the
next step in a pathway leading to a
cellular response.
At this point, the G-protein acts as a
GTPase enzyme to hydrolyze GTP to
make GDP making itself inactive. It is now
available for reuse.
Tyrosine-Kinase Receptors (page 212)
What is Tyrosine? ______________ What is a Kinase? ___________________
Receptor extends through the cell membrane.
Intracellular part functions as a “kinase”, which transfers P from ATP to amino
acid tyrosine on a substrate protein
Often activate several different pathways at once, usually 10 or more (a single
binding of signal triggers multiple pathways to occur, helping regulate
complicated functions such as cell division and cell growth).
Abnormal receptors (meaning they function in the absence of a signal
molecule) contribute to some kinds of cancer.
How the Tyrosine-kinase receptor works: (page 212)
1. Ligand binding causes two receptor polypeptides to aggregate forming a
“dimer” which activates the tyrosine kinase region (inside cell).
2. Each tyrosine kinase adds a P (from ATP) to a tyrosine on the other
polypeptide.
3. Now activated, the receptor is recognized by specific relay proteins inside
the cell. The relay proteins bind to a specific phosphorylated tryosine causing
it to change shape…this triggers a transduction pathway leading to a cellular
response.
Before
signal binds,
receptors
exist as
individual
polypeptides
6
6
Ion-Channel Receptors (page 213)
Receptors that act as “gates” (open or close in response to
chemical signal) that either allows or blocks the flow of ions
such as Na+ or Ca2+ through a channel in the receptor.
Ex - nervous system signals.
neurotransmitter released by one nerve
cell to send signal to a neighboring one.
It binds to ion channel receptor causing
gate to open…letting ions into cell.
This triggers an electrical signal
(ions are charged atoms) down
the receiving cell.
There are some gated ion channels that
are controlled by electrical signals
instead of ligands. These are
“voltage-gated ion channels.”
Chapter 48
Intracellular Receptors (page 210, then continues on 213)
Proteins located in the cytoplasm or nucleus that receive a
signal that CAN pass through the cell membrane.
Activated protein turns on genes in nucleus.
Ex - steroids (hormones)
they are lipids, so they can
diffuse through if not too big.
NO - nitric oxide
Enters nucleus
with hormone
attached
Chapter 45
When in the nucleus, the activated
receptor protein acts as a transcription
factor to turn on a specific gene
B. Signal Transduction
1. The further amplification and movement of a signal in the
cytoplasm to target molecules.
2. Often has multiple steps using “relay proteins” such as
Protein Kinases.
a. Remember, a protein kinase is any enzyme that
transfers P from ATP to a protein.
b. About 2 % of our genes are for Protein Kinases.
c. When a protein is phosphorylated, it changes shape
and “activates” it.
d. Usually adds P to amino acids Serine or Threonine.
3. Protein phosphatases are enzymes that remove
phophate groups from proteins.
a. this is called “dephosphylation”
b. this “inactivates” the protein kinases.
c. this provides a way to turn off the signal transduction
pathway when the initial signal is no longer present.
d. this also makes the protein kinases available for
reuse.
4. Secondary Messengers
a. Small water soluble non-protein molecules or ions that
pass on a signal.
b. Spread throughout cell by diffusion.
c. Activates relay proteins.
d. cyclic AMP (cAMP) and Ca2+ ions are widely used
A form of AMP made directly from ATP by Adenylyl cyclase.
Enzyme
in
Short lived -found
converted
back to AMP.
the cell
Activates a membrane
number of Protein Kinases.
Works in
response
to signal
Doesn’t stay in
cytoplasm long
Figure 11.11 in
your book.
Page 216
Epinephrine
Adenylyl
cyclase
G Proteincoupled
receptor
ATP
cAMP
Protein
kinase A
Hydrolysis of glycogen
e. Calcium Ions
More widely used than cAMP.
Used as a secondary messenger in both G-protein pathways
and tyrosine-kinase receptor pathways. Pathway causes an
increase in cytosolic concentration
Normally Ca2+ are actively transported out of the cell and
imported from the cytosol into the ER, mitochondria,
chloroplasts
Ca2+ release involves IP3 (inositol triphophate) or DAG
(diacylglycerol)
Used in plants, animal muscle contraction, secretion of certain
substances, and cell division
f. Inositol Triphosphate (IP3) and diacylglycerol (DAG)
These messengers are made by cleavage of a certain kind of
phospholipid in the plasma membrane.
Sent to Ca2+ channel on the ER.
Allows flood of Ca2+ into the cytoplasm from the ER.
C. Cellular Responses
1. Cytoplasmic Regulation
a. Rearrangement of the cytoskeleton.
b. Opening or closing of an ion
channel.
c. Alteration of cell metabolism.
2. Transcription Regulation in the nucleus
(DNA --> RNA).
a. Activating protein synthesis for new
enzymes.
b. Transcription control factors are
often activated by a Protein Kinase.
c. can turn a gene on or off.
3. Amplification
a. Protein Kinases often work in a cascade with each
being able to activate several molecules.
b. Result - from one signal, many molecules can be
activated because each protein stays in the active
form long
enough to
process
many
molecules
before they
become
inactive
again.
4. Question
a. If liver and heart cells both are exposed to ligands,
why does one respond and the other not?
b. Different cells have different collections of receptors,
relay proteins, and proteins needed to carry out the
response.
5. Alternate Explanation