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Cell Communication
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The “Cellular Internet”
• Biologists have discovered some universal
mechanisms of cellular regulation that involve
cell-to-cell communication.
•External signals are converted into responses within the cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evolution of Cell Signaling
• 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.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
a/
Methods used by Cells to Communicate
• Cell-Cell communication
•
Cell Signaling using chemical messengers
1. Local signaling over short distances
•
Cell-Cell Recognition
•
Local regulators
– Paracrine (growth factors)
– Synaptic (neurotransmitters)
2. Long distance signaling
•
Hormones
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cell-Cell Communication
• 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
Cell-Cell Communication
 Animal cells use gap junctions to send
signals
Cells must be in direct contact
 Protein channels connecting two
adjoining cells

Gap junctions
between animal cells
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Cell-Cell Communication
 Plant cells use plasmodesmata to send
signals
Cells must be in direct contact
 Gaps in the cell wall connecting the two
adjoining cells together

Plasmodesmata
between plant cells
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Local Signaling: Cell-Cell Recognition
• In local signaling, animal cells may communicate via direct
contact
• Membrane bound cell surface molecules
• Glycoproteins
• Glyolipids
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: Local Regulators
• In other cases, animal cells
– Communicate using local regulators
– Only work over a short distance
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.
Long-distance Signaling: Hormones
• In long-distance signaling
– Both plants and animals use hormones
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
Figure 11.4
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
C body cells.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Long-Distance Signaling
 Nervous System in Animals

Electrical signals through neurons
 Endocrine System in Animals

Uses hormones to transmit messages
over long distances
 Plants also use hormones
Some transported through vascular
system
 Others are released into the air

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The Three Stages of Cell Signaling
• Earl W. Sutherland (1971)
– Discovered how the hormone epinephrine acts on cells
• Sutherland suggested that cells receiving signals went
through three processes
– Reception
– Transduction
– Response
• Called 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
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
Three Stages of Cell Signaling
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
1 Reception
Receptor
The receptor and signaling molecules
fit together (lock and key model,
induced fit model, just like enzymes!)
Signaling
molecule
 Signaling molecule binds to the
receptor protein
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Three Stages of Cell Signaling
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
Receptor
2nd
Messenger!
Relay molecules in a signal transduction pathway
Signaling
molecule
 The signal is converted into a form that
can produce a cellular response
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Three Stages of Cell Signaling
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
Can be catalysis, activation of a gene,
triggering apoptosis, almost anything!
 The transduced signal triggers a
cellular response
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Signal Transduction Animation
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campbell_biology_7/media/interactiv
emedia/activities/load.html?11&A
 http://www.wiley.com/legacy/college/bo
yer/0470003790/animations/signal_tran
sduction/signal_transduction.htm
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There are three most common types of
membrane receptor proteins.
 G-protein coupled receptors
 Receptor tyrosine-kinases
 Ion channel receptors
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1. Reception
• A signal molecule, a ligand, binds to a receptor
protein in a lock and key fashion, causing the
receptor to change shape.
Most receptor proteins
are in the cell
membrane but some are
inside the cell.
The G-protein is a
common membrane
receptor.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
G-Protein Coupled Receptors
are often involved in diseases
such as bacterial infections.
G-Protein Receptors
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
Enzyme
GDP
2
1
CYTOPLASM
G protein
(inactive)
GDP
GTP
Activated
enzyme
i
GTP
GDP
P
4
3
Cellular response
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Inactive
enzyme
• Receptor tyrosine kinases
Signal-binding site
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
Ion Channel Receptors
 Very important in
1
Gate
closed
Ions
Signaling
molecule
(ligand)
the nervous system
 Signal triggers the
opening of an ion
channel
depolarization
 Triggered by
neurotransmitters
Ligand-gated
ion channel receptor
Plasma
membrane
2
Gate open

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Cellular
response
3
Gate closed
2. Transduction
• Transduction: Cascades of molecular
interactions relay signals from receptors to
target molecules in the cell
• Multistep pathways
– Can amplify a signal (Amplifies the signal by
activating multiple copies of the next component in the
pathway)
– Provide more opportunities for coordination
and regulation
• At each step in a pathway, the signal is
transduced into a different form, commonly a
conformational change in a protein.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fig. 11-9
Signaling molecule
Receptor
Transduction:
Activated relay
molecule
Inactive
protein kinase
1
A Phosphorylation
Cascade
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
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Pi
PP
Active
protein
Cellular
response
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 transduction stage of signaling is often a
multistep process that amplifies the signal.
About 1%
of our
genes are
thought to
code for
kinases.
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/bc_campbell_biology_7/media/in
teractivemedia/activities/load.ht
ml?11&C
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Small Molecules and Ions as Second Messengers
•
Secondary messengers
–
Are small, nonprotein, water-soluble molecules or ions that act as
secondary messengers.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cyclic 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
GTP
ATP
cAMP
Protein
kinase A
Cellular responses
Figure 11.10
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cyclic AMP
• 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
Fig. 11-11
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Transduction in a
G-protein pathway
Second
messenger
Protein
kinase A
Cellular responses
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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
Calcium is an important
EXTRACELLULAR
FLUID
ATP
Plasma
membrane
Ca2+
pump
Mitochondrion
second messenger
because cells are able to
regulate its concentration
in the cytosol
Nucleus
CYTOSOL
Ca2+
pump
ATP
Key
Ca2+
pump
Endoplasmic
reticulum (ER)
High [Ca2+]
Low [Ca2+]
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Other second
messengers such as
inositol triphosphate and
diacylglycerol can
trigger an increase in
calcium in the cytosol
1 A signal molecule binds
2 Phospholipase C cleaves a
to a receptor, leading to
plasma membrane phospholipid
activation of phospholipase C. called PIP2 into DAG and IP3.
EXTRACELLULAR
FLUID
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+
Cellular
response
Ca2+
(second
messenger)
Figure 11.12
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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.
Growth factor
3. Response
Receptor
Reception
 Many possible
outcomes
 This example
shows a
transcription
response
Phosphorylation
cascade
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
DNA
Gene
NUCLEUS
mRNA
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Transduction
Response
Signaling
molecule
 Specificity of the
Receptor
signal


The same signal
molecule can
trigger different
responses
Many responses
can come from
one signal!
Relay
molecules
Response 1
Response 2
Response 3
Cell A. Pathway leads Cell B. Pathway branches,
to a single response. leading to two responses.
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 The signal
can also
trigger an
activator or
inhibitor
 The signal
can also
trigger
multiple
receptors and
different
responses
Activation
or inhibition
Response 4
Response 5
Cell C. Cross-talk occurs Cell D. Different receptor
between two pathways.
leads to a different response.
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Response- cell signaling leads to regulation
of transcription (turn genes on or off) or
cytoplasmic activities.
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Long-distance Signaling
Intracellular signaling includes hormones that are
hydrophobic and can cross the cell membrane.
Once inside the cell, the
hormone attaches to a
protein that takes it
into the nucleus where
transcription can be
stimulated.
Testosterone acts as a
transcription factor.
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• Steroid hormones
– 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.
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 binding
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Any Questions??
Can You Hear Me Now?
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Two systems control all physiological processes
1. Nervous System –
neurosecretory glands in
endocrine tissues secrete hormones.
2. Endocrine System
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Human Endocrine System
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Major Vertebrate Endocrine Glands Their Hormones
(Hypothalamus–Parathyroid glands)
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Figure 45.6b Hormones of the hypothalamus and pituitary glands
Neurosecretory cells in endocrine organs and tissues
secrete hormones. These hormones are excreted
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into
the circulatory system.
Stress and the
Adrenal Gland
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http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/site
s/dl/free/0072437316/120109/bio48.swf::Action%20of%
20Epinephrine%20on%20a%20Liver%20Cell
Figure 45.4 One chemical signal, different effects
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Figure 45.9 Hormonal control of calcium homeostasis in mammals
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m/thelifewire/content/ch
p42/4202003.html
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Figure 45.10 Glucose homeostasis maintained by insulin and glucagon
http://vcell.ndsu.nodak.edu/animations/regulatedsecre
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tion/movie.htm
Cellular Communication Review
Denise Green
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REVIEW: Signal-transduction pathway
 Definition: Signal on a cell’s surface is converted into a
specific cellular response
 Local signaling (short distance):
√ Paracrine (growth factors)
√ Synaptic (neurotransmitters)
 Long distance: hormones
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Stages of cell signaling
 Sutherland (‘71)
 Glycogen depolymerization by epinephrine
 3 steps:
•Reception: target cell detection
•Transduction: single-step or series of changes
•Response: triggering of a specific cellular response
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• G-protein-linked receptors
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
Protein phosphorylation
 Protein activity




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regulation
Adding phosphate from
ATP to a protein
(activates proteins)
Enzyme: protein kinases
(1% of all our genes)
Example: cell
reproduction
Reversal enzyme:
protein phosphatases
Second messengers
 Non-protein signaling




pathway
Example: cyclic AMP
(cAMP)
Ex: Glycogen
breakdown with
epinephrine
Enzyme: adenylyl
cyclase
G-protein-linked
receptor in membrane
(guanosine di- or triphosphate)
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Cellular responses to signals
 Cytoplasmic activity
regulation
 Cell metabolism
regulation
 Nuclear
transcription
regulation
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2010 Free Response Question
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The three stage of cellular signaling:
Reception, Transduction, and Response.

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