Download Chapter 11: Cell Communication 11.1 External signals are

Chapter 11: Cell Communication
11.1 External signals are converted to responses
within the cell
Evolution of Cell Signaling
 Type of yeast identifies their mates by chemical
signaling
 a sex secretes a factor which binds to receptors
proteins on α cells
 α sex secretes α factor which binds to receptors
on a cells
 Received signal is converted to cellular response
through series of steps = signal transduction
pathway
o Molecular details are similar in yeast and
animal cells = evolved from common
ancestor
o Think that they first evolved in ancient
prokaryotes and single celled eukaryotes
 Without entering the cells the two mating factors
cause the cells to grow toward each other and bring about cellular changes
o Results in fusion/mating of two cells of opposite type
 New a/α cell has all the genes of both original cells = a combo of genetic
resources that provides advantages to cell’s descendants
o Arise by cell division
 Cell signaling is vital in microbial world
o Bacteria secretes molecules that are detected by other bacterial cells
o Concentration sensed by bacteria allows them to monitor local
density of cells = quorum sensing
 Allows bacterial populations to coordinate behavior to carry
out activities only productive when performed by cells in
synchrony
Local and Long-Distance Signaling
 Cells in a multicellular organism communicate via chemical messengers
targeted for adjacent or nonadjacent cells
 Cell junctions directly connect cytoplasms of adjacent cells allowing
dissolved signaling substances in the cytosol to pass freely between cells
 Animal cells may communicate via direct contact through cell-cell
recognition (important in embryonic development and immune response)
 Local regulators = messenger molecules secreted by signaling cells that only
travel short distances
o Growth factors consist of compounds that stimulate target cells to
grow and divide
Paracrine signaling = when numerous cells simultaneously
receive and respond to molecules of growth factor produced by
a single nearby cell
o Synaptic signaling occurs in the nervous system
 Electric signal along a nerve cell triggers secretion of
neurotransmitter molecules carrying chemical signal
 Molecules diffuse across the synapse (space between nerve cell
and target cell) triggering response
Use hormones for long-distance signaling
o Endocrine signaling = hormone signaling in animals
 Specialized cells release hormone molecules which travel via
the circulatory system to target cells
o Plant growth regulators = hormone signaling in plants
 Reach targets by moving through cells or diffusing through air
as a gas
Transmission of a signal through the nervous system is also long distance
o Electrical signal travels length of nerve cell and is then converted back
to a chemical signal when a signaling molecule is released and rosses
the synapse to another nerve cell  converted back to electric signal
 Can travel this way down a series of nerve cells
 Can quickly travel great distances
When a cell encounters a secreted signaling molecule, its ability to respond
depends on whether it has a specific receptor molecule that can bind
o Info conveyed by binding (the signal) must then be changed into
another form inside the cell before it can respond
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The Three Stages of Cell Signaling: A Preview
 Earl Sutherland investigated how hormone epinephrine/adrenaline
stimulates breakdown of glycogen in liver and skeletal muscle cells
o Breakdown releases sugar glucose 1-phosphate, which is converted to
glucose 6-phosphate which the cell can use for energy production or
released as glucose to fuel cells throughout the body
o Effect: mobilization of fuel reserves used as fight or flight
o Discovered that epinephrine stimulates breakdown by activating a
cytosolic enzyme, but when added to a test-tube with enzyme and
substrate, no breakdown occurred
 Could only activate when hormone was added in intact cells
 Proved epinephrine doesn’t directly interact with enzyme
 Proved plasma membrane is involved in signal transmission
1. Reception: target cell’s detection of signaling molecule coming from outside
the cell
a. Chemical signal is detected when signaling molecule binds to the
receptor protein located at the cell’s surface or inside the cell
b. Binding of the signaling molecule changes the receptor protein
initiating transduction
2. Transduction: converts signal to a form that can bring cellular response
a. Sometimes occurs in single step, often requires sequence of changes
in a series of molecules (signal transduction pathway)
i. Relay molecules = molecules in pathway
3. Response: any cellular activity triggered by transduced signal
a. Helps ensure that crucial activities occur in the right cells at the right
time in proper coordination with activities of other cells
11.2: Reception: A signaling molecule binds to a receptor protein, causing it to
change shape
Receptors in the Plasma Membrane
 Reception of the signal depends on the receiver
o Hormones only target cells that detect and react to it
o A receptor protein on/in target cell allows it to hear and respond to
the signal
o Signaling molecule is complementary in shape to specific site on
receptor and attaches there
 Behaves as a ligand, a molecule that specifically binds to
another molecule
 Causes receptor protein to undergo shape change
 Most are plasma membrane proteins
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Most water-soluble signaling molecules bind to specific sites on receptor
proteins that span plasma membrane
o Transmembrane receptor transmits info from extracellular
environment to inside the cell by changing shape/aggregating when
ligand binds
3 types of cell surface transmembrane receptors:
o G protein-coupled receptors works with help of G protein
which binds to GTP (energy rich)
 Vary in binding sites and types of G proteins inside cell
 Similar in structure, with α helices
 Widespread/diverse functions (embryonic
development, sensory reception, diseases)
1. When GDP is bound its inactive
2. G protein binds to inactivated receptor on cytoplasm side
causing GTP to displace GDP and activating G protein
3. Activated G protein dissociates from receptor binding to
enzyme, altering its shape and activity
a. Enzyme can trigger next step
4. Changes in enzyme and G protein are temporary
a. G protein hydrolyzes its bound GBT to GBD inactivating
it and leaving the enzyme
o Receptor tyrosine kinases have enzymatic activity
 Kinase = enzyme that catalyzes transfer of phosphate groups
 Tyrosine kinase = part of receptor protein extending into
cytoplasm catalyzing transfer of phosphate group from ATOP
to tyrosine amino acid on substrate protein
 Can activate 10+ different transduction pathways and cellular
responses (more than one can be triggered at once) to help
regulate cell growth and reproduction
 Abnormal receptor tyrosine kinases linked to cancer
1. Before signaling molecule binds the receptors exist as
individual units (monomers)
2. Binding of a signaling molecule causes two receptor monomers
to associate closely with each other forming a dimer
3. Dimerization activates tyrosine kinase region
a. Each tyrosine kinase adds a phosphate from ATP to
tyrosine on tail of other monomer
4. Receptor is fully activated
a. Recognized by specific relay proteins which bind to
phosphorylated tyrosine  structural change activating
bound protein
b. Triggers transduction pathway  cellular response
o Ion channel receptors = membrane
receptor region that acts as a gate
when the receptor changes shape
 When a signaling molecule
binds as a ligand to receptor
protein gate opens/closes
allowing/blocking flow of ions
 Important in the nervous
system in flow of ions
triggering electrical signal
down cells
1. Gate is closed
2. Ligand binds opening the gate
a. Specific ions can flow
through channel and
quickly change
concentration of ion in
the cell
b. May directly affect cell
activity
3. Ligand dissociates from
receptor closing the gate
Intracellular Receptors found in cytoplasm or
nucleus
 Chemical messenger passes through target
cell’s plasma membrane to reach receptor
o Can do this because they are
hydrophobic or small enough to cross
hydrophobic interior of membrane
 Steroid hormones can do this: ex:
testosterone
o Secreted by cells of the testes, travels
through blood and enters cells all
over the body
o Only cells with receptor molecules for
testosterone respond
 Hormone bonds to receptor
protein activating it and
entering
 Activated hormone-receptor complex turns
on genes by acting as a transcription factor,
controlling which genes are turned on
11.3: Transduction: Cascades of molecular interactions relay signals from
receptors to target molecules in the cell
Overview
 Transduction stage is usually a multistep pathway with steps involving the
activation of proteins by addition/removal of phosphate groups, release of
small molecules/ions to act as messengers, etc.
 Benefit of multiple steps is the possibility of greatly amplifying a signal
 If some molecules in a pathway transmit signal to numerous molecules at the
next step in the series it can result in a large number of activated molecules
at the end of the pathway
 Multistep pathways provide more opportunities for coordination and
regulation than simpler systems  fine tuned response
Signal Transduction Pathways
 Binding of specific signaling molecule to a receptor in plasma membrane
triggers first step in chain of molecular interactions leading to response
 Signal activated receptor activates another molecule on and on until the
protein that produces cellular response is activated
 Relay molecules = molecules that relay a signal from receptor to response
 Signal is usually transduced into a different form like a shape change in a
protein brought about by phosphorylation
Protein Phosphorylation and Dephosphorylation
 Can activate a protein by adding phosphate groups to it
 Phosphorylation and dephosphorylation of proteins is a widespread cellular
mechanism for regulating protein activity
 Protein kinase = enzyme transfers phosphate groups from ATP to protein
o Most cytoplasmic protein kinases act on proteins other than
themselves and phosphorylate either serine or threonine
o Many relay molecules in signal transduction pathways are protein
kinases and act on other protein kinases in the pathway
 Signal is transmitted my cascade of protein phosphorylations bringing a
shape change resulting from interaction of new phosphate groups with
charged/polar amino acids activating or deactivating the protein
 Abnormal kinase activity can help develop cancer
 Protein phosphatases = enzymes that can quickly remove phosphate groups
from proteins = dephosphorylation
o Deactivates kinases providing the mechanism for turning off signal
transduction pathway when initial signal is no longer present
o Make protein kinases reusable, allowing cell to respond again
 Phosphorylation-dephosphorylation = molecular switch turning activities
on/off as required
o Activity depends on balance between active kinase and active
phosphatase molecules
Small Molecules and Ions as Second Messengers
 Signaling pathways also involve second messengers = small, non-protein
water-soluble molecules
o Because they’re small and water soluble they can spread through the
cell by diffusion
o Participate in pathways initiated by both G protein-coupled receptors
and receptor tyrosine kinases
o Relay proteins are sensitive to cytosolic concentration of second
messengers
 Cyclic AMP/cAMP = second messenger involved in epinephrine pathway
o Binding of epinephrine to plasma membrane of a liver cell increases
cytosolic concentration of cAMP
o Adenylyl cyclase = enzyme in plasma membrane that converts ATP to
cAMP in response to extracellular signal (epinephrine)
 Epinephrine doesnt stimulate directly-receptor protein it binds
to activates adenylyl cyclase catalyzing synthesis of cAMP
o cAMP broadcasts signal to cytoplasm
 Doesn’t last long bc phosphodiesterase converts cAMP to AMP
o Many other hormones and signaling molecules also trigger formation
of cAMP
o Immediate effect of cAMP is usually activation of protein kinase A 
phosphorylates other proteins depending on cell type
o Further regulation: G protein systems inhibit adenylyl cyclase
 Different signaling molecule activates a different receptor
which activates inhibitory G protein
o Involved in how microbes cause disease: ex: Cholera
 Acquire bacteria from drinking contaminated water
 Bacteria form biofilm on lining of small intestine, produce toxin
 Toxin is an enzyme that chemically modifies G protein involved
in regulating salt and water secretion
 G protein cant hydrolyze GTP to GDP its stuck in active form
continuously stimulating adenylyl cyclase to make cAMP
 High concentration of cAMP causes
intestines to secrete salts  water
follows by osmosis  diarrhea
o Used in medicine: cyclic GMP relaxes smooth
muscle cells in artery walls  inhibition of
hydrolysis of cGMP to GMP prolongs signal
increasing blood flow (helps chest pain,
erectile dysfunction…)
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Calcium Ions (Ca2+) and Inositol Triphosphate (IP3)
o Some signaling molecules in animals induce responses in their target
cells via signal transduction pathways that increase cytosolic
concentration of calcium ions
 Causes variety of responses: muscle contraction, secretion, cell
division…
o Hormonal and environmental stimuli can cause brief increases in
cytosolic Ca2+ concentration triggering signaling pathways in plants
o Cells use as a second messenger in G protein and receptor tyrosine
kinase pathways
o Functions as a second messenger because its concentration in the
cytosol is normally much lower than the concentration outside the cell
o Ca2+ is actively imported out of the cell and actively imported from
cytosol into ER by protein pumps so Ca2+ in ER is higher than cytosol
Because cytosolic calcium level is low a small change in
absolute numbers of ions represents large change in Ca2+
o In response to a transduction pathway signal cytosolic Ca2+ level may
rise due to a mechanism that releases Ca2+ from the cell’s ER
 Pathway leading to Ca2+ release involves inositol triphosphate/
IP3 and diacylglycerol (DAG) produced by cleavage of
phospholipid in plasma membrane
o IP3 stimulates release of calcium from the ER
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