Download Cell A.

Ch. 11: Cell Communication
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Ch. 11: Cell Communication
• Coordinate activities
– Universal mechanisms among all living cells
– Provides evidence for evolutionary relatedness of all
life.
– Ligand – chemical signals
• water soluble
• too large to cross the plasma membrane
• Signal-transduction Pathway –
• signal on cell’s surface - converts into a specific
cellular response - a series of steps
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.2 Communication between mating yeast cells
 factor
1 Exchange of
Receptor
mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.

a
Yeast cell,
mating type a
a factor
Yeast cell,
mating type 
2 Mating. Binding
of the factors to
receptors induces
changes in the
cells that lead to
their fusion.

a
3 New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and  cells.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
a/
Direct Contact:
• Plant cells – thru plasmodesmata
• Animal cells - between membrane-bound cell
surface molecules.
• importance - embryonic development, immune
response.
• Ex. growth factors- stimulate nearby target cells
to grow/multiply.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.3 Communication by direct contact between cells
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
(b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local or long distance:
1. paracrine signaling - direct contact
transmitting cells release local regulators
• cell junctions connect to the cytoplasm of
adjacent cells.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.4 Local and long-distance cell
communication in animals
Local signaling
Target cell
Secreting
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.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local:
2. synaptic signaling –
neurotransmitter - diffuses across a synapse to
a very close cell (target cell)
-neurotransmitter stimulates the target cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.4 Local and long-distance cell
communication in animals
Local signaling
Target cell
Secreting
cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
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.
Target cell
is stimulated
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Long distance:
3. hormonal signaling – long distance signaling;
plants and animals
• plant hormone - ethylene (C2H4)
– 6 atom hydrocarbon passes through cell walls.
– promotes fruit ripening
– regulates growth
• Mammal hormone - Insulin
– regulates blood sugar levels in mammals
– a protein with thousands of atoms.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.4 Local and long-distance cell
communication in animals
Local signaling
Long-distance signaling
Target cell
Secreting
cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
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.
Endocrine cell
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
3 stages of cell signaling:
• 1. reception
• 2. transduction
• 3. response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.5 Overview of cell signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
1. Reception • a chemical signal binds to a cellular protein
receptor
– cell’s surface or inside cell.
• Target cell recognizes the signal molecule –
due to a complimentary shape
• Receptor undergoes a shape change –
allowing interaction with other molecules
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.5 Overview of cell signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Signal
molecule
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
2. Transduction:
A Signal-Transduction Pathway
• Initiation - Receptor protein changes
• Converts signal to a form that brings about a
specific cellular response
• Ex. Epinephrine binding to a receptor protein in
a liver cell’s plasma membrane
– leads to activation of glycogen phosphorylase
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.5 Overview of cell signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction pathway
Signal
molecule
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
3. Response –
Transduction signal triggers a specific cellular
response such as:
– catalysis by an enzyme
– rearrangement of the cytoskeleton
– activation of specific genes in the nucleus
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.5 Overview of cell signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Hormone receptors
• are intercellular
• their ligands are nonpolar
– travel between lipids in plasma membrane
– steroids, thyroid hormones
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.6 Steroid hormone interacting with an
intracellular receptor
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
hormone testosterone
passes through the
plasma membrane.
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
3 The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
DNA
mRNA
NUCLEUS
1 The steroid
4 The bound protein
stimulates the
transcription of
the gene into mRNA.
New protein
5 The mRNA is
translated into a
specific protein.
CYTOPLASM
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
I.
Reception:
3 major types of membrane receptors:
1. G-protein-linked receptors
2. Tyrosine kinase receptors
3. Ion-channel receptors.
• Most signal receptors are plasma
membrane proteins.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.7 Exploring Membrane Receptors
Signal-binding site
G-PROTEIN-LINKED RECEPTORS
Segment that
interacts with
G proteins
G-protein-linked
receptor
Plasma Membrane
Activated
receptor
Signal molecule
GDP
CYTOPLASM
G-protein
(inactive)
Enzyme
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inactive
enzyme
1. G-protein-linked receptor •
a receptor protein associated with a G protein
- G protein acts as an on/off switch.
• GDP - bound to the G protein (inactive)
• ligand binds to the G protein receptor,
• G protein binds GTP (active)
• G protein dissociates from receptor
• diffuses along the membrane
• binds to an enzyme, altering its activity.
• enzyme triggers next step leading to cellular response.
–
•
G protein can also act as GTPase enzyme - hydrolyze GTP to
GDP.
turns G protein off.
–
leaves the enzyme
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.7 Exploring Membrane Receptors
Signal-binding site
G-PROTEIN-LINKED RECEPTORS
- embryonic development.
-Vision and smell in humans depend on these proteins.
-Bacterial infections - cholera and botulism interfere with Gprotein function.
Segment that
interacts with
G proteins
•binds many epinephrine and neurotransmitters.
G-protein-linked
receptor
Plasma Membrane
Activated
receptor
Signal molecule
GDP
CYTOPLASM
G-protein
(inactive)
Enzyme
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inactive
enzyme
TYROSINE KINASE RECEPTORs
RECEPTOR TYROSINE KINASES
Signal-binding site
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
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
Tyr P
Tyr P
P Tyr
Tyr P
P Tyr
Tyr P
Tyr P
P Tyr
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
2. tyrosine-kinase receptor –
• work in pairs – dimers
• Ligands bind to two receptors - dimerization
– kinase - an enzyme that catalyzes the transfer
of phosphate groups
– P from 6ATP’s + tyrosine tails
– Activates cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
TYROSINE KINASE RECEPTORs
RECEPTOR TYROSINE KINASES- coordinate cell growth/reproduction.
Signal-binding site
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
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
Tyr P
Tyr P
P Tyr
Tyr P
P Tyr
Tyr P
Tyr P
P Tyr
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
3. Ligand-gated ion channel • Ligand binds to receptor protein
– gate opens - allow ions in, ex. Na+ or Ca2+
– ligand dissociates - channel closes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Ion Channel Receptors
Ex. nervous
system:
•Ions trigger
electrical
signals
•propagate
down the
receiving cell
Signal
molecule
(ligand)
Gate
Gate
close
Closed
Ions
Ligand-gated
ion channel receptor
Plasma
Membrane
Gate open
Cellular
response
Gate close
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
ION CHANNEL RECEPTORS
II. Transduction:
• Cascade of relay signals from receptors to
relay molecules in the cell
– greatly amplifies the signal
– few signal molecules - large cellular response.
– mostly proteins
– signal is transduced into a different form
• often by a conformational change
– by transferring a P - phosphorylation.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.8 A phosphorylation cascade abnormal activity of
one of the kinases
can cause abnormal
cell
growth/reproduction
and contribute to the
development of
cancer
Signal molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
1 A relay molecule
activates protein kinase 1.
2 Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
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.
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
P
Active
protein
kinase
2
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Ossilation between phosphorylation and dephosphorylation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
Active
protein
Cellular
response
Second Messengers – involved in signal
transduction pathways
1. cyclic AMP
NH2
N
N
O
O
O
N
N
–
O P O P O P O Ch2
O
O
O
NH2
NH2
O
Pyrophosphate
P Pi
O
CH2
Phoshodiesterase
ATP
O
HO P O CH2
Requires constant supply of ligand to remain in the
cyclic form
activated receptor activates adenylyl cyclaseconverts ATP to cAMP.
Maintains high levels of cellular activity
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
O
H2O
OH
Cyclic AMP
Figure 11.9 Cyclic AMP
N
N
O
O
O
P
O
N
N
N
N
Adenylyl cyclase
O
OH OH
N
N
OH OH
AMP
1. cAMP
Figure 11.10 cAMP as a second messenger in a
G-protein-signaling pathway
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
GTP
ATP
“Fight or flight”
hormone from
adrenal medulla
Second
cAMP messenger
Protein
kinase A
Cellular responses
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cholera toxin
modifies G
protein in
intestinal cells,
cAMP is
constantly active,
causing intestinal
cells to release
salts, dehydration
occurs
Signal Transduction Scenario
3.Sugar activates a G protein-linked receptor on the tongue
stimulating adenylyl cyclase to produce cAMP. cAMP
activates protein kinase A which closes K+ channels and
causes Ca 2+ ions to enter the cell. The influx of Ca2+ causes
the release of a neurotransmitter form the tongue & provides
the “sweet” taste from some candy.
6.Activation of a G-protein-linked receptor stimulates adenylyl
cyclase to convert ATP to cAMP. cAMP activates protein
kinase A which initiates a phosphorylation cascade that ends
with the phosphorylation of glycogen phosphorylase and
releases glucose from glycogen.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
2. Ca2+ (2nd messenger)
•
Animal cells –
•
Increases may cause contraction of muscle
cells
Plant cells –
–
increase triggers responses
•
pathway for greening in response to light.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Transduction Scenerio
4.Sunlight is detected by a plant cell which opens Ca2+
channels in the plasma membrane. The Ca2+ ions
activate protein kinase 2 which phosphorylates
transcription factors for de-etiolation genes (genes
that cause greening of the plant).
7.The neurotransmitter acetylcholine activates a ligandgated ion channel causing Na+ ions to enter a
muscle cell. Because the muscle cell is now
“charged,” Ca2+ ions are released, which bind to a
muscle protein allowing a muscle to contract.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.11 The maintenance of calcium ion
concentrations in an animal cell – a secondary messenger
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+
pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
ATP
Ca2+
Endoplasmic
reticulum (ER)
pump
Key
High [Ca2+]
Low [Ca2+]
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Ca2+ concentration in the
cytosol is usually much lower
than that in the extracellular
fluid and ER.
Protein pumps in the plasma
membrane and the ER
membrane, driven by ATP
move Ca2+ from the cytosol
into the extracellular fluid and
into the lumen of the ER.
Mitochondrial pumps, driven
by chemiosmosis, move Ca2+
into mitochondria when the
calcium level in the cytosol
rises significantly.
Function: Muscle cell contractions,
cell division, growth factors,
neurotransmitters.
3. Diacylglycerol (DAG) and inositol trisphosphate
(IP3).
• DAG and IP3 are created when a
phospholipase cleaves membrane
phospholipid PIP2 (inositol)
• phospholipase - activated by G protein or
tyrosine-kinase receptor.
• IP3 activates a gated-calcium channel,
releasing Ca2+ from the ER.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.12 Calcium and IP3 in signaling pathways
1
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
2 Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
3 DAG functions as
a second messenger
in other pathways.
Signal molecule
(first messenger)
G protein
DAG
GTP
PIP2
G-protein-linked
receptor
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Various
proteins
activated
Ca2+
CYTOSOL
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
Cellular
responses
Ca2+
(second
messenger)
5 Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
6 The calcium ions
activate the next
protein in one or more
signaling pathways.
Signal Transduction Scenerio
1.Activation of a tyrosine-kinase receptor causes
phopholipase C to cleave PIP2 forming IP3
and DAG from the cell membrane. IP3 then
binds to a ligand-gated ion channel on the ER
causing the release of calcium ions, which
bind to calmodulin & causes the cytoskeleton
to change shape.
8.The binding of a sperm to an egg initiates a G
protein pathway that releases IP3 & DAG.
This releases Ca2+ ion from the ER which
cause the cortical reaction and allow for the
formation of the fertilization envelope.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
III. Response:
A signal (ligand)
• Opens or closes ion channels.
• regulates enzyme activity
• act as transcription factors - turn specific genes
on/off (nucleus)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.13 Cytoplasmic response to a signal: the
stimulation of glycogen breakdown by epinephrine
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Amplifies the
hormonal
signal
Transduction
Inactive G protein
Active G protein (102 molecules)
Activates about
100 G protein
molecules
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.14 Nuclear responses to a signal: the
activation of a specific gene by a growth factor
Growth factor
Local regulator
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
mRNA
Signal Transduction Scenerio
2.Activation of a steroid hormone receptor
causes the hormone/receptor complex to
travel into the nucleus and turn on genes
(initiate transcription) needed for making
muscle protein.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.15 The specificity of cell signaling
Signal
molecule
Receptor
Relay
molecules
Response 1
Response 2 Response 3
Cell A. Pathway leads
to a single response
Cell B. Pathway branches,
leading to two responses
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Response 5
Cell D. Different receptor
leads to a different response
Scaffolding proteins
–
Rather than relying on diffusion of large relay molecules
–
pathways are linked together physically by scaffolding
–
enhances speed, accuracy, and efficiency
Signal
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Three
different
protein
kinases