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Cell Communication
Cellular Communication
by direct cell-cell contact
Cellular Communication
(a) Communicating cell junctions.
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
(b) Cell-cell recognition.
“Cell phone”
Figure 11.3
Cellular Communication —
Cellular Communication
via chemical messengers
1.
Release: initiator cell secretes (exocytosis) a chemical
messenger (signal molecules).
Reception: messenger molecules bind to receptors (binding
proteins) on target cells.
Transduction: binding of signal molecule to receptor causes a
change in the structure and activity of the receptor protein.
Response: the altered receptor protein initiates a change in the
enzymatic and/or transcriptional activity of the target cell.
2.
3.
4.
EXTRACELLULAR
FLUID
PLASMA MEMBRANE
2 Reception
CYTOPLASM
3 Transduction
Receptor
Relay molecules in a signal
transduction pathway
Signal molecule
4 Response
Activation
of cellular
response
Figure 11.5
Major Classes of
Biochemical Signal Molecules
I.
Amino acid origin
a)
b)
c)
d)
II.
growth factor, cytokine) diffuses
to nearby target cells.
3. Endocrine: the messenger
(hormone) diffuses into the
bloodstream to travel to target
cells all over the body.
4. Exocrine: the messenger
(pheromone) diffuses outside of
the organism’s body to travel to
another organism.
Tyrosine family of amines
I = iodine
Amino acids
Modified amino acids — bioamines
Oligopeptides
Proteins
Fatty acid origin
a)
b)
III.
Derived from cholesterol — steroids
Derived from arachidonic acid — prostaglandins
Dissolved gases
a)
b)
c)
Heyer
Chemical Messengers & Receptors
the messenger
One cell releases a molecule 1. Synapse:
(neurotransmitter) diffuses
(messenger) that initiates a
across a small gap between a
neuron and its target cell.
change in another cell by
binding to a protein receptor 2. Paracrine: the messenger (local
regulator, paracrine factor,
on that target cell.
Note iodine
Nitric oxide (NO)
Carbon monoxide (CO)
Ethylene (H 2C=CH 2)
1
Cell Communication
Mechanisms of Messenger Action
• Hydrophilic signal molecules — most amino acid class
– Water soluble.
– Short half-life: minutes
– Do not enter target cells. Act as ligand by binding to protein
receptor on cell surface.
• Lipophilic signal molecules — most fatty acid class
– Water insoluble. Must be transported in plasma by carrier proteins.
– Carrier proteins also protect hormone from degradation. Half-life
longer: 1–2 hours.
– Released from carrier protein to diffuse across cell membrane into
target cells. Act by binding to intracellular protein receptors.
Signal transduction pathways via
second messengers
Act as cofactors/coenzymes to modulate
intracellular enzyme activity
Signal molecule (first messenger)
Steroids
Mechanisms of Hydrophilic
Signal Molecule Action
• Hydrophilic signal molecules — most amino acid class
– Water soluble.
– Short half-life: minutes
– Do not enter target cells. Act as ligand by binding to protein
receptor on cell surface.
1. Since the signal molecule (first messenger) does not enter the cell,
the receptor/ligand complex causes a second messenger to be
produced or released within the cell.
2. This second messenger acts as a coenzyme/cofactor to regulate
cellular enzymes fi change the activity of the cell.
Common second messengers
Act as cofactors/coenzymes to modulate
intracellular enzyme activity
++
1. Ca
NH
NH
2
N
O
Receptor
Activated relay
molecule (second messenger)
2. cAMP
O
N
O
–
O P O P O P O Ch 2
O
OOO-
Inactive
enzyme
Active
enzyme
Heyer
ATP
3. IP3
4. DAG
Phospholipid (PIP 2)
in membrane bilayer
N
N
2
N
N
Adenylyl cyclase
N
N
Figure 11.9
Tryptophan family of amines
CH 2
O
O O
P
Pyrophosphate
O- O
P Pi
OH OH
OH
Phospholipase C
Cyclic AMP
Inisotol triphosphate
(IP 3)
+
Diacylglycerol
(DAG)
2
Cell Communication
1. G-protein mediated
2. Tyrosine kinase
3. Receptor-ion channels
G-protein-mediated Membrane Receptors
Signal-binding site
Segment that
interacts with
G proteins
1.
2.
3.
4.
5.
6.
7.
G-protein-linked
Receptor
Signal molecule binds receptor.
Receptor-ligand bind G-protein; G-protein releases GDP.
G-protein binds GTP; receptor releases G-protein–GTP.
G-protein–GTP moves along membrane to inactive enzyme.
Enzyme is activated; second messenger is produced.
G-protein hydrolyzes P i from GTP; enzyme releases G-protein–GDP.
Enzyme inactivated again. Go to #1.
Activated
Receptor
Plasma Membrane
Signal molecule
Inactivated
enzyme
GDP
G-protein
(inactive)
CYTOPLASM
Enzyme
GDP
GTP
Activated
enzyme
GTP
Inactivated
enzyme
Figure 11.7
Membrane Receptor Types
GDP
Pi
Cellular response
Membrane protein activity mediated via GDP/GTP-binding proteins (G-proteins).
Second messenger: cyclic-AMP
Second messengers: IP3 / DAG / Ca++
Tyrosine Kinase Receptors
Receptor-ion channels
Signal
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
Ions
Plasma
Membrane
– Direct: receptor is the gate.
– Indirect: receptor opens/closes
separate gate protein via G-proteins.
Gate open
Cellular
response
Gate closes
• Kinase (“enzyme activation enzyme”): phosphorylase
• Tyrosine kinase: phosphate added to tyrosine residues of enzyme proteins
Heyer
• Chemically-mediated ion gates
• Signal molecule binds receptor;
gated channel opens or closes
• Opening gates causes voltage
change in cell.
– Na + gate: depolarizes
– K+ or Cl – gate: hyperpolarizes
Figure 11.7
3
Cell Communication
Cascade reactions amplify signal
Phosphorylation Cascade
Scaffolding proteins
or cytoskeleton may
hold group of cascade
enzymes in a complex.
Signal molecule
Activated relay
molecule
Receptor
Active
protein
kinase
1
Inactive
protein kinase
2
2 Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
ATP
PP
Inactive
protein kinase
3
5 Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse.
P
Active
protein
kinase
2
ADP
Pi
Figure 11.8
1 A relay molecule
activates protein kinase 1.
ATP
Pi
de
sca
ca
on
lati
ory
ph
os
Ph
Inactive
protein kinase
1
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
Active
protein
kinase
3
ADP
PP
Inactive
protein
ATP
Pi
PP
ADP
P
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
P
Active
Cellular
protein
response
Intracellular Receptors for Lipophilic
Signal
Molecules
1. Steroid diffuses across
membrane into cell
2. Intracellular
receptor/steroid complex
binds to DNA
3. Transcription factor —
turns genes on/off
4. Change nature of the cell
(Longer-lasting effect)
Reception
• One epinephrine
signal molecular
momentarily binding
to the membrane
receptor
• Results in the
production of
100,000,000
glucose-1-phosphate
molecules in the cell.
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (10 2 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (10 2)
ATP
Cyclic AMP (10 4)
Inactive protein kinase A
Active protein kinase A (10 4)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (10 6)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
Figure 11.13
Mechanisms of Messenger Action
• Hydrophilic signal molecules — most amino acid class
– Bind to membrane receptors on cell surface
– Primary effect: turn enzymes on/off Æ D activity of cell.
– Secondary effect: enzymes may produce or activate transcription
Growth factor Reception
factors Æ turn genes on/off.
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
Active
transcription
transcription
factor
P
factor
DNA
Response
Gene
NUCLEUS
Mechanisms of Messenger Action
• Hydrophilic signal molecules — most amino acid class
– Bind to membrane receptors on cell surface
– Primary effect: turn enzymes on/off Æ D activity of cell.
– Secondary effect: enzymes may produce or activate transcription
factors Æ turn genes on/off.
• Lipophilic signal molecules — most fatty acid class
– Bind to intracellular receptors in cytoplasm or nucleoplasm
– Primary effect: turn genes on/off Æ D nature of cell.
– Secondary effect: gene expression may produce or activate
enzymes Æ turn metabolic pathways on/off.
Heyer
mRNA
Figure 11.14
Modulation of signal effect
•Priming (upregulation)
Signal bindsÆ more receptors synthesized
Ø
more hormone can bind cell
•Desensitization (downregulation)
Prolonged exposure to high signal molecule
levels can reduce receptor expression.
* Downregulation may be avoided by pulsatile
secretion of the messenger.
•Receptor-mediated endocytosis
Receptor-ligand complex internalized on vesicle
to enhance duration of effect.
4
Cell Communica,on • Dendrites: increase surface area of cell
body to receive signals.
Electrochemical communication
Rapid signaling to specific targets
• Cell body: location of nucleus and most
organelles.
Neuron — cell extends axon to release
• Axon: conducts electrochemical
impulses.
signal molecule at local site
• Termini: transmit message to target cell.
Neuron: A Nerve Cell
Action Potential
Neuron Requirements
by voltage-gated ion channels
Function requires:
1. 
Membrane potential:
– Voltage (millivolts) across plasma membrane
2.  Excitability:
– The ability to undergo rapid changes in membrane potential
in response to stimuli
3.  Conduction:
– Propagation of a series of excitations along the plasma
membrane
4.  Transmission:
– Release and reception of signal molecules
(neurotransmitters)
1 
Na+ channels open
•
2 
Na+ rushes in (making inside positive)
Na+ channels close. K+ channels open
•
3  K+
K+ rushes out (making it negative)
channels close. Na+ / K+ pumps resegregate ions.
c.f., Fig. 48.10 Conduction of electrochemical signals in
neuron axons
• Nerve impulse is a series of action potentials propagated in sequence down the neuron.
• Nerves are NOT wires!
• Nerve impulses are NOT electricity!
• Only the axons of neurons
conduct the nerve impulse.
• Initiated at the hillock,
Fig. 48.11 Heyer • Propagate toward the axon terminus
5 Cell Communica,on Transmission:
Synapses & Local Signaling
• Synaptic terminals secrete signal molecules
– neurotransmitter — e.g. acetylcholine
• NT binds to receptors on postsynaptic cell.
Fig. 48.12 Synaptic Transmission:
release of signal molecule
Synaptic Transmission:
Reception
• Action potentials conducted down axon to terminus.
• Voltage-Gated Ca2+ channels open.
– Ca2+ rapidly enters terminus
• (down concentration and charge gradient).
– Ca2+ acts as cofactor for enzymes to trigger rapid
fusion of synaptic vesicles è exocytosis of
neurotransmitter (NT) into synaptic cleft.
• NT release is rapid because many vesicles form
fusion-complexes at “docking sites.”
Synaptic Transmission:
release & reception
• NT receptors open ion channels, allowing in Na+
– this initiates a response in the target cell
• Released NTs diffuse across synaptic cleft.
• NT (ligand) binds to specific receptor proteins in
postsynaptic cell membrane.
• Chemically-regulated gated ion channels open.
– If Na+ gates è depolarization
è stimulation.
– If K+ or Cl– gates è hyperpolarization
è inhibition.
• Neurotransmitter inactivated to end transmission.
Neurotransmitters
• Different types used by different neurons.
• NTs are broken down & recycled by enzymes.
– dopamine, serotonin, endorphins, even NO
• They can excite or inhibit transmission.
• Chemicals (e.g., LSD, insecticides, opiates)
– mimic neurotransmitters
– block neurotransmitters
– block receptor sites
– block breakdown enzymes
Fig. 48.16 Heyer 6