Chapter 11
Cell communication
How cells detect, process, and respond to chemical
signals send from other cells or from changes in
the physical environment ?
• Overview: The Cellular Internet
• Cell-to-cell communication
– Is absolutely essential for multicellular organisms
– External signals are converted into responses
within the cell
Ex. Yeast cells --- Identify their mates by cell signaling
Cell signaling evolved early in the history of life
Saccharomyces cerevisiae “yeast”
--- identify their mates by chemical signaling
1 Exchange of
mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.
2 Mating. Binding
of the factors to
receptors
induces changes
in the cells that
lead to their
fusion.
 factor
Receptor

a
Yeast cell,  factor Yeast cell,
mating type a
mating type 

a
Two sex,(mating type)
Without actually entering the
cells, the receptor-bound
molecules of the two mating
factors cause the cells to grow
toward each other and bring
about other cellullar changes.
3 New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and a cells.
a/
Figure 11.2
The process by which a signal on a cell’s surface is
converted into a specific cellular response is a series
of steps
--- called a signal-transduction pathway
• Signal transduction pathways
– Convert signals on a cell’s surface into cellular responses
– Are similar in microbes and mammals, suggesting an early
origin
– Cells in a multicellular organism --- communicate via
chemical messengers
• Animal and plant cells
– Have cell junctions that directly connect the
cytoplasm of adjacent cells
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
• In local signaling, animal cells
– May communicate via direct contact
Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.
• In other cases, animal cells
– Communicate using local regulators
Paracrine signaling:
--- the transmitting cell secretes molecules of a local regulator
a substance that influences cells in the vicinity.
Growth factor
neurotransmitter
Local signaling
Target cell
Secretory
vesicle
Figure 11.4 A B
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.
• In long-distance signaling
– Both plants and animals use hormones
* Endocrine signaling: (animal cells)
Long-distance signaling
Blood
vessel
Endocrine cell
--- specialized cells release hormone molecules
into vessels of the circulatory system.
* In plants, hormones sometimes travel in vessels
Hormone travels
in bloodstream
to target cells
but more often reach their targets by moving
through cells or by diffusion
through the air as a gas.
Target
cell
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Figure 11.4 C
The plant hormone ethylene, a gas
that promotes fruit ripening and
helps regulate growth.
(C2H4)
What happens when a cell encounters a signal ?
The signal must be recognized by a specific receptor molecule,
and the information it carries must be changed into another
form-transduced-inside the cell before the cell can respond.
The three stages of cell signaling are reception,
transduction, response
Earl W. Sutherland (Nobel Prize in 1971)
How the animal hormone epinephrine stimulates
breakdown of the storage polysaccharide glycogen
within liver and skeletal muscle cells.
Glycolysis:
Glycogen
Glucose-1-phosphate
Glucose-6-phosphate
glucose
Epinephrine
Enzyme:
Glycogen phosphorylase
1. When epinephrine was added to a
Test-tube mixture containing the
phosphorylase and its substrate, glycogen
no depolymerization occurred
2. Epinephrine could activate glycogen phosphorylase
only when it was added to a solution containing
intact cells.
Glycogen
Glucose-1-phosphate
Glucose-6-phosphate
glucose
1. Epinephrine does not interact directly with
the enzyme responsible for glycogen
breakdown.
2. The plasma membrane is somehow involved in
transmitting the epinephrine signal.
Relay molecules
1. Catalysis by an enzyme
2. Rearrangement of the
cytoskeleton
3. Activation of specific
genes in the nucleus
Signal reception and the initiation of transduction
 yeast cell only “heard” the signals by its prospective mates, a cells.
The signal receptor is the identity tag on the target cell.
A signal molecule binds to a receptor protein, causing the
protein to change shape.
* The term for a small
molecule that specifically
binds to a larger one
ligand
Key & lock
receptor
Conformational change
receptor
activation
Most signal receptors are plasma membrane proteins
Receptor transmits information from the extracellular
environment to the inside of the cell by changing
shape or aggregating when a specific ligand binds to it.
Three major types of membrane receptors:
1. G-protein-linked receptors
2. tyrosin-kinase receptors
3. ion-channel receptors
1. G-protein-linked receptors
--- a plasma membrane receptor
--- works with the help of a protein called a G protein
--- vary in their binding sites for recognizing signal
molecules and for recognizing different G proteins
G-protein-linked receptor:
--- involved in diseases.
cholera 霍亂
pertussis 百日咳
--- widespread and diverse in
functions.
* mouse embryogenesis
* sensory reception
(vision and smell)
視覺
Signal-binding site
G protein: GDP bound --- inactive
GTP bound --- active
嗅覺
G-protein-linked
Receptor
Plasma Membrane
Activated
Receptor
Signal molecule
GDP
CYTOPLASM
Segment that
interacts with
G proteins
G-protein
(inactive)
GDP
Enzyme
1.
GTP
2.
Activated
enzyme
Figure 11.7
GTP
GDP
Pi
3.
Cellular response
Figure 11.7
4.
Inctivate
enzyme
2. Tyrosine-Kinase Receptors
( have enzymatic activity 酵素活性: tyrosin kinase)
--- a type of receptor specialized for triggering more
than one signal-transduction pathway at once.
Signal-binding sitea
Signal
molecule
Signal
molecule
Helix in the
Membrane
Tyr
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Tyr
Dimer
1. Polypeptide aggregation
2. Phosphorylation of the
Activated
relay proteins
Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr
P Tyr
Tyr P
Tyr
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Inactive
relay proteins
receptor
Cellular
response 1
Cellular
response 2
The ability of a single ligand-binding event to trigger so many
pathways is a key difference between these receptors and
G-protein-linked receptors.
Ligand independent activation of tyrosin-kinase receptor
Mutation (突變)
Signal
molecule
(ligand)
Gate
closed
Ions
Ion-channel receptors:
Ligand-gated ion channels
Ligand-gated
ion channel receptor
Plasma
Membrane
* Nervous system
Gate open
Cellular
response
Gate close
Figure 11.7
Not all signal receptors are membrane proteins !!
Intracellular receptors :
--- in the cytosol or nucleus of target cells.
--- * hydrophobic : steroid hormones
tyroid hormones
ex. Testosterone (one steroid hormone)
--- secreted from testis
* small molecules : nitric oxide (NO)
Activated testosterone receptor
Transcription factors
In nucleus:
ex, estrogen receptors
transcription
translation
Signal-transduction pathways
Relay molecules
--- multistep pathway
--- signal amplification
1. Catalysis by an enzyme
2. Rearrangement of the
cytoskeleton
3. Activation of specific
genes in the nucleus
Protein phosphorylation
Conformational change

Protein phosphorylation:
--- a widespread cellular mechanism for regulating protein activity.
Protein kinase: (磷酸激酶)
- an enzyme that transfers phosphate
Protein phosphatase: (去磷酸酶)
- an enzyme that remove phosphate
groups from proteins.
groups from ATP to a protein.
ATP
ADP
kinase
A
phosphatase
inactive
Pi
A
P
active
Protein kinase:
tyrosin kinase
serine/threonine kinase
1%
A phosphorylation cascade
Not all components of signal-transduction pathway are proteins !!
Many signaling pathways also involve small, nonprotein,
water-soluble molecules or ions
Second messengers
* Spread by “diffusion”
* Participate in pathways initiated by both G-protein-linked
receptors and tyrosin-kinase receptors.
* Including cyclic AMP and calcium ions (Ca2+).
Cyclic AMP
Cyclic adenosine monophosphate; cyclic AMP; cAMP
NH2
N
N
O
O
O
N
N
–
O P O P O P O Ch2
O
O
O
Figure 11.9
N
N
O
Pyrophosphate
P Pi
O
CH2
Phoshodiesterase
O
OH
Cyclic AMP
N
N
O
HO P O CH2
O
O
P
O
N
N
N
N
Adenylyl cyclase
O
OH OH
ATP
NH2
NH2
O
H2O
OH OH
AMP
• Many G-proteins
–
Trigger the formation of cAMP, which then acts as a
second messenger in cellular pathways
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
* Cholera
--- Vibrio cholerae
--- produce a toxin, which
modifies a G protein
GTP
ATP
cAMP
Protein
kinase A
Cellular responses
Figure 11.10
* Some are inhibitory G protein
which inhibit adenylyl cyclase.
involved in regulating
salt and water secretion.
Neurotransmitters
Growth factors
hormones
Cytosolic concentration
of calcium ions (Ca2+) 
Muscle cell contraction
secretion
Cell division
Ca2+
More widely used than
cAMP as a second
messenger
Ca2+ concentration in the cytosol is normally much lower
than the concentration outside the cell.
10,000X
Figure 11.11
EXTRACELLULAR
FLUID
ATP
Plasma
membrane
Ca2+
pump
Mitochondrion
* Diacylglycerol (DAG)
* Inositol trisphosphate
Nucleus
(IP3)
CYTOSOL
Ca2+
pump
ATP
Ca2+
Endoplasmic
reticulum (ER)
pump
Key
High [Ca2+]
Low [Ca2+]
* Calcium and IP3 in signaling pathways.
1
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
2
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
PIP2
G-protein-linked
receptor
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Various
proteins
activated
Ca2+
Cellular
response
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.
Figure 11.12
5
Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
6
The calcium ions
activate the next
protein in one or more
signaling pathways.
Concept 11.4
Response: cell signaling leads to regulation of cytoplasmic
activities or transcription
Growth factor
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Reception
Receptor
Transduction
Inactive G protein
Active G protein (102 molecules)
Phosphorylation
cascade
Transduction
Inactive adenylyl cyclase
cytoplasmic
response
Active adenylyl cyclase (102)
nucleus
response
CYTOPLASM
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)
Inactive
transcription
factor
Active
transcription
factor
P
DNA
Gene
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
Response
NUCLEUS
mRNA
Why are there often so many steps between a signaling
event at the cell surface and the cell’s response ?
Two important benefits:
1. Signal amplification
2. The specificity of response
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
* At each catalytic step in the cascade,
the number of activated products is
much greater than in the preceding
step.
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
Figure 11.13
Glucose-1-phosphate
(108 molecules)
Signaling pathways with a multiplicity of steps have
two important benefits:
1. amplify the signal
2. contribute to the specificity of response
The specificity of cell signaling
epinephrine
Liver cell
Glycogen breakdown
heart cell
contraction
The response of a particular cell to a signal depends on its
particular collection of signal receptor proteins, relay
proteins, and proteins needed to carry out the response.
Signal
molecule
Receptor
Relay
molecules
Cell A. Pathway leads
to a single response
Response 1
Cell C. Cross-talk occurs
between two pathways
Response
2
3
Cell B. Pathway branches,
leading to two responses
Cell D. Different receptor
leads to a different response
Activation
or inhibition
Response 4
Figure 11.15
Response
Response 5
Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes
• Scaffolding proteins
–
Can increase the signal transduction efficiency
Signal
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Figure 11.16
Three
different
protein
kinases
A key to a cell’s continuing receptiveness to regulation is
the reversibility of the changes that signals produce.
Termination of the Signal
How ?
• Signal response is terminated quickly
–
By the reversal of ligand binding
–
The relay molecules return to their
inactive forms.