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Ch. 11 Cell Communication
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
11.1 External signals are converted into responses
within the cell
• Signal transduction pathways
– Convert signals on a cell’s surface into cellular
responses
– Are similar in microbes and mammals,
suggesting an early origin
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Primitive Example in Yeast
Yeast cells Identify their mates by cell 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
3 New a/ cell.
Figure 11.2
The nucleus of
the fused cell
includes all the
genes from the
a and a cells.
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a/
Quorum Sensing in Bacteria – A Vocal Majority!
Cell Density can trigger bacterial behavior i.e.
biolumenence & pathogenicity
Avenues for new antibiotic drugs?
TED talks
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local (cell-to-cell) and Long-Distance (organ-toorgan) Signaling via Chemicals
• Local signaling via direct contact between
animal cells
Figure 11.3 (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 signaling via local chemical regulators
Local signaling
Target 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.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Target cell
is stimulated
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Cellular adaptations that circumvent cell membranes
• 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.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Long-Distance signaling via hormones
– Hormone: chemical messenger produced in
one place but used in another
– Both plants and animals use hormones
Endocrine
cell
Bloo
d
vess
el
Hormone
travels
in bloodstream
to target cells
Targ
et
cell
(c) Hormonal signaling.
Specialized
endocrine cells secrete
hormones
into body fluids, often the blood.
Hormones may reach virtually
all
body Cummings
cells.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin
The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland
– Discovered how the hormone epinephrine
(adrenalin) acts on cells
3 main stages of cell signaling:
– Reception
– Transduction
– Response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• 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
Figure 11.5
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
11.2: Signal Reception - intracellular or plasma
membrane
• The binding between signal molecule (ligand)
– And receptor is highly specific
• A conformational change in a receptor
– Is often the initial transduction of the signal
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Intracellular Receptors vs. Membrane Receptors
• Intracellular receptors
– Are cytoplasmic or nuclear proteins
• There are three main types of membrane
receptor proteins
– G-protein-linked
– Tyrosine kinases
– Ion channel proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
So where do signal molecules “know” where to go?
• Signal molecules that are small or hydrophobic
– And can readily cross the plasma membrane
use intracellular receptors
Signal molecules that are polar/hydrophilic cannot
Cross plasma membrane and therefore use
membrane receptors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Steroid hormones most common signals to enter cell
• Steroid hormones are non-polar and cross
membrane to bind to intracellular receptors
Hormone
EXTRACELLULAR
(testosterone) FLUID
1 The steroid
hormone testosterone
passes through the
plasma membrane.
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
3 The hormone-
DNA
receptor complex
enters the nucleus
and binds to specific
genes.
mRNA
4 The bound protein
NUCLEUS
stimulates the
transcription of
the gene into mRNA.
New protein
5 The mRNA is
Figure 11.6
CYTOPLASM
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
translated into a
specific protein.
3 Main types of membrane receptors
Type 1. G-protein-linked receptors work with
GTP,GDP, GMP GDP< GMP
Signal-binding site
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
Figure 11.7
Cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inctivate
enzyme
Membrane receptor type 2
tyrosine kinases
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
Activated
relay proteins
Figure 11.7
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)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Membrane Receptor type 3
• Ion channel receptors
Signal
molecule
(ligand)
Gate
closed
Ions
Ligand-gated
ion channel receptor
Plasma
Membrane
Gate open
Cellular
response
Gate close
Figure 11.7
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11.3 Signal Transduction
• Cascades of molecular interactions relay
signals from receptors to target molecules in
the cell
• Multistep pathways
– Can amplify a signal
– Provide more opportunities for coordination
and regulation
– Transduction usually involves a conformational
change in a protein shape (form/function)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Phosphorylation and Dephosphorylation
• Many signal pathways
– Include phosphorylation cascades
• In this process
– A series of protein kinases add a phosphate to
the next one in line, activating it
– Phosphatase enzymes then remove the
phosphates
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
A phosphorylation cascade
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
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.
Figure 11.8
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
P
Active
protein
kinase
2
ADP
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
ATP
ADP
Pi
PP
P
Active
protein
Cellular
response
The Role of Second Messengers in Cascades
• Second messengers
– Are small, nonprotein, polar molecules or ions
that help to conduct signal
– 2 most common 2nd messengers:
cAMP, Ca2+
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Cyclic AMP : A Closer Look
• Cyclic AMP (cAMP)
– Is made from ATP
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
Figure 11.9
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O
OH
Cyclic AMP
N
N
O
HO P O CH2
O
O
P
O
N
N
N
N
Adenylyl cyclase
O
OH OH
N
N
O
H2O
OH OH
AMP
Remember G proteins?
• Many G-proteins trigger the formation of cAMP
or cGMP, which then act as a second
messengers in cellular pathways
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
or
guanylyl
cyclase
GTP
ATP
cAMP
Protein
kinase A
Cellular responses
Figure 11.10
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Calcium ions and Inositol Triphosphate (IP3)
• Calcium, when released into the cytosol of a
cell
– Acts as a second messenger in many different
pathways
IP3 triggers release of Ca2+ in cytosol
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Calcium Pumps EVERYWHERE!
• Calcium is an important second messenger
– Because cells are able to regulate its
concentration in the cytosol
EXTRACELLULAR
FLUID
ATP
Plasma
membrane
Ca2+
pump
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
ATP
Key
Figure 11.11
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Ca2+
pump
Endoplasmic
reticulum (ER)
High [Ca2+]
Low [Ca2+]
11.4: Response via regulation of cell activities
• In the cytoplasm
– Signaling
pathways
regulate a
variety of
cellular
activities
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
– i.e. Glycogen
hydrolysis
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
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Nuclear Response (via lipid hormones)
• Other pathways
– Regulate genes by activating transcription
factors that turn genes on or off
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription Active
transcription
factor
factor
P
Response
DNA
Gene
Figure 11.14
NUCLEUS
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mRNA
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
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Three
different
protein
kinases
Termination of the Signal
• Signal response is terminated quickly
– By the reversal of ligand (signal molecule)
binding
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings