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Fig. 11-1
Chapter 11: Cell
Communication
11.1 Involved in regulation within living organisms.
• How cells detect, process, and respond to
chemical signals from other cells
• Signal transduction pathway =process by
which a signal on a cell’s surface is converted
to a specific cellular response.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
1. Local Regulators-substance that influences nearby
cells
a. Paracrine signaling: one signal cells sends out
message to many nearby cells.
Ex. growth factors: stimulate cells to grow and
multiply
b. Synaptic signaling: neurotransmitter crosses
synapse and triggers nerve impulse
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-5ab
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
(b) Synaptic signaling
c. Identification of Mates
1. Yeast mating types =
a (secretes a factor)
and α (secrete α
factor)
2. Factors bind to
receptors on opposite
mating type
3. Cells grow towards
each other and fuse
4. Result = a/α cell with
all of the genes of
both mating types
2. Hormonal Signaling: greater distance
a. animals:
hormones
released from
glands travel
through blood
stream
b. plants: hormones
may diffuse
through cells or air
as a gas (ethylene
gas)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
3. Direct contact:
a. Dissolved
substances move
through cytosol from
cell to cell through
openings
(plasmodesmata,
gap junctions)
b. Direct contact
between molecules
on cell surfacesimportant in
embryonic
development
The Three Stages of Cell Signaling
• Earl W. Sutherland (Nobel Prize in 1971)
discovered how the hormone epinephrine acts
on cells
1. Reception: chemical signal detected when it
binds to a cellular protein on surface, changing
receptor protein in some way
2. Transduction: converts signal into a form that
can bring about a cellular response (usually
occurs in a series of steps-signal transduction
pathway)
3. Response- transduced signal triggers a response
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-6-3
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signaling
molecule
11.2 Signal Reception and the Initiation
of Transduction
• Signal molecule or ligand binds to receptor
protein causing it to change conformation.
– A shape change in a receptor is often the initial
transduction of the signal
– Very specific, like lock and key or
enzyme/substrate
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
I. Receptors in the Plasma Membrane
1. G protein-coupled receptor: plasma
membrane receptor that works with the help of
a G protein
a. Anatomy:
1. Receptor: seven α-helices spanning the
membrane
2. The G protein acts as an on/off switch:
3. GUANINE nucleotides: GDP is bound=inactive
GTP is bound =active
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7a
Signaling-molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor
Receptors in the Plasma Membrane
b. Physiology:
1.
Ligand binds to receptor
2.
Receptor conformation changes
3.
Receptor binds to an inactive G protein causing GDP to
be displaced by GTP.
4.
Activated G protein binds to another protein (usually
and enzyme) and changes its activity
5.
GTPase enzyme hydrolyzes GTP to GDP and the G
protein is inactive
Up to 60% of all medicines work because of their
effects on G proteins!
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7b
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4
Inactive
enzyme
2. Tyrosine-Kinase Receptors
a.
Tyrosine-Kinase catalyzes the transfer of phosphate groups
from ATP to the amino acid tyrosine on a substrate protein.
b. How it works:
1.
Before signal molecule binds, receptor = individual polypeptides
2.
Ligand binding causes the two polypeptides to combine
3.
Tyrosine-Kinases on each polypeptide activated
4.
Each phosphorylates the tyrosines in the tail of the other
5.
The receptors are now activated and they turn on active relay
proteins
6.
The relay proteins trigger many different transduction pathways.
Abnormal tryosine-kinase receptors that aggregate without a
ligand cause some kinds of cancer!
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7c
Ligand-binding site
Signaling
molecule (ligand)
Signaling
molecule
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLASM
Dimer
1
2
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
P Tyr
P Tyr
Tyr
Tyr
P
6 ATP
Activated tyrosine
kinase regions
6 ADP
Tyr
Tyr
P Tyr
Tyr
P
Tyr
P Tyr
P Tyr
Tyr
P
P
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine kinase
Inactive
relay proteins
3
4
Cellular
response 1
Cellular
response 2
3. Ion Channel Receptors
a. Ligand-gated ion channel =protein pores in
the membrane
b. Open or close in response to a chemical
signal
c. Allows or blocks flow of specific ions, such as
Na+ or Ca2+
d. Important to nerve impulse transition
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7d
1 Signaling
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
2
Ions
Plasma
membrane
Gate open
Cellular
response
3
Gate closed
4. Intracellular Receptors
a. Some receptor proteins are found in the
cytosol or nucleus
b. Chemical messengers can readily cross the
target cell’s membrane
c. Bind to receptors which turn on genes
d. ex. steroid hormones (lipids) and small
gaseous molecules (NO2)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-8-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-2
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
11.3. Signal Transduction Pathway: like falling
dominoes
1. Multistep pathways which relay signals from receptors
to cell responses
2. Benefit = amplification
3. Relies on protein conformation changes by
phosphorylation by protein kinases
4. Signal transmitted by a cascade of protein
phosphorylations.
5. The effects of protein kinases are rapidly reversed by
protein phosphates (dephosphorylation)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
Pi
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Second Messengers
1. Small, non-protein, water-soluble molecules or
ions that spread throughout a cell by diffusion
(Ca2+ and Cyclic Amp)
2. Cyclic Amp (adenosine monophosphate)
a. extracellular signal causes adenylyl cyclase
to convert ATP to cAMP.
b. cAMP then activates a protein kinase which
causes a cascade of reactions
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-10
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate
P
ATP
Pi
cAMP
AMP
Fig. 11-11
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
3. Calcium Ions and Inositol Triphosphate (IP3)
a. Calcium (Ca2+) is an important second
messenger because cells can regulate its
concentration
b. Ca2+ ions stored in the ER
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-12
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
High [Ca2+]
Low [Ca2+]
Ca2+
pump
c. Process:
1. Signal molecule binds to a receptor
2. Phospholipase C activated
3. Cleaves special phospholipid (PIP2) into the
second messengers DAG (diacylglycerol) and IP3
4. IP3 diffuses through cytosol and binds to gated
channel
5. Ca2+ flows out of ER
6. Ca2+activate next protein in signal pathway
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-13-3
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2+
Ca2+
(second
messenger
)
Cellular
responses
11.4. Cellular Responses to Signals
1. May regulate activities in the cytoplasm
a. Enzyme activity
b. Rearrangement of the cytoskeleton
2. May regulate transcription
a. Activate transcription factors
b. Turn on specific genes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-14
Growth factor
Reception
Receptor
Phosphorylatio
n
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Fine-Tuning of the Response
• Multistep pathways have two important
benefits:
– Amplifying the signal (and thus the response)
– Contributing to the specificity of the response
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Amplification
1. Elaborate enzyme cascades amplify the cell’s
response to a signal
2. At each step in the cascade, the number of
activated products is greater
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Specificity
1. Different kinds of cells have different proteins!
2. Response to a signal will vary based on
receptors, relay molecules, and proteins
needed to carry out the response.
3. Same signal molecule can cause different
responses in different cells.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-17
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses.
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different response.
Apoptosis (programmed cell death) integrates
multiple cell-signaling pathways
• Apoptosis is programmed or controlled cell
suicide
• A cell is chopped and packaged into vesicles
that are digested by scavenger cells
• Apoptosis prevents enzymes from leaking out
of a dying cell and damaging neighboring cells
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-19
2 µm
Fig. 11-20
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Ced-4 Ced-3
Receptor
for deathsignaling
molecule
Inactive proteins
(a) No death signal
Ced-9
(inactive)
Cell
forms
blebs
Deathsignaling
molecule
Active Active
Ced-4 Ced-3
Activation
cascade
(b) Death signal
Other
proteases
Nucleases
Apoptotic Pathways and the Signals That Trigger
Them
• Caspases are the main proteases (enzymes
that cut up proteins) that carry out apoptosis
• Apoptosis can be triggered by:
– An extracellular death-signaling ligand
– DNA damage in the nucleus
– Protein misfolding in the endoplasmic
reticulum
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Apoptosis evolved early in animal evolution
and is essential for the development and
maintenance of all animals
• Apoptosis may be involved in some diseases
(for example, Parkinson’s and Alzheimer’s);
interference with apoptosis may contribute to
some cancers
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-21
Interdigital tissue
1 mm