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Chapter 11

Cell Communication

PowerPoint Lectures for


Biology, Seventh Edition
Neil Campbell and Jane Reece

Lectures by Chris Romero


Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: The Cellular Internet

• Cell-to-cell communication
– Is absolutely essential for multicellular
organisms

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings


• Biologists
– Have discovered some universal mechanisms
of cellular regulation

Figure 11.1
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• Concept 11.1: External signals are converted
into responses within the cell

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Evolution of Cell Signaling
• Yeast cells
– Identify their mates by cell signaling
1 Exchange of α factor
mating factors. Receptor
Each cell type
secretes a
mating factor a α
that binds to
receptors on
the other cell
type. Yeast cell, α factor Yeast cell,
mating type a mating type α
2 Mating. Binding
of the factors to
receptors
induces changes a α
in the cells that
lead to their
fusion.
3 New a/α cell.
The nucleus of
the fused cell
includes all the
a/α
genes from the
Figure 11.2 a and a cells.

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• Signal transduction pathways
– Convert signals on a cell’s surface into cellular
responses
– Are similar in microbes and mammals,
suggesting an early origin

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Local and Long-Distance Signaling
• Cells in a multicellular organism
– Communicate via chemical messengers

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• Animal and plant cells
– Have cell junctions that directly connect the
cytoplasm of adjacent cells
Plasma membranes

Gap junctions Plasmodesmata


between animal cells 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.

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• 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.

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• In other cases, animal cells
– Communicate using local regulators
Local signaling

Target cell Electrical signal


along nerve cell
triggers release of
neurotransmitter

Neurotransmitter
Secretory diffuses across
vesicle synapse

Local regulator
diffuses through Target cell
extracellular fluid is stimulated
(a) Paracrine signaling. A secreting cell acts (b) Synaptic signaling. A nerve cell
on nearby target cells by discharging releases neurotransmitter molecules
molecules of a local regulator (a growth into a synapse, stimulating the
factor, for example) into the extracellular target cell.
Figure 11.4 A B fluid.

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• 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

(c) Hormonal signaling. Specialized


endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
Figure 11.4 C body cells.
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The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland
– Discovered how the hormone epinephrine acts
on cells

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• Sutherland suggested that cells receiving
signals went through three processes
– Reception

– Transduction

– Response

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• Overview of cell signaling

EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane

1 Reception 2 Transduction 3 Response

Receptor

Activation
of cellular
response
Relay molecules in a signal transduction pathway

Signal
molecule

Figure 11.5

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• Concept 11.2: Reception: A signal molecule
binds to a receptor protein, causing it to
change shape

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• 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

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Intracellular Receptors
• Intracellular receptors
– Are cytoplasmic or nuclear proteins

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• Signal molecules that are small or hydrophobic
– And can readily cross the plasma membrane
use these receptors

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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
Receptor membrane
2 Testosterone binds
protein to a receptor protein
Hormone- in the cytoplasm,
receptor activating it.
complex

3 The hormone-
receptor complex
enters the nucleus
and binds to specific
DNA genes.
mRNA 4 The bound protein
stimulates the
transcription of
NUCLEUS New protein the gene into mRNA.

5 The mRNA is
translated into a
specific protein.
Figure 11.6 CYTOPLASM

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Receptors in the Plasma Membrane
• There are three main types of membrane
receptors
– G-protein-linked

– Tyrosine kinases

– Ion channel

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• G-protein-linked receptors
Signal-binding site

Segment that
interacts with
G proteins

G-protein-linked Activated Inctivate


Plasma Membrane Signal molecule
Receptor Receptor enzyme

GDP
G-protein GDP GTP
CYTOPLASM (inactive) Enzyme

Activated
enzyme

GTP
GDP
Pi

Cellular response
Figure 11.7
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• Receptor tyrosine kinases
Signal Signal-binding sitea
molecule
Signal
αHelix in the molecule
Membrane

Tyr Tyr
Tyr Tyr Tyr Tyr
Tyrosines Tyr Tyr
Tyr Tyr Tyr Tyr
Tyr Tyr
Tyr Tyr Tyr Tyr

Receptor tyrosine
CYTOPLASM kinase proteins Dimer
(inactive monomers)

Activated
relay proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P
Tyr P
response 1
Tyr Tyr P Tyr Tyr P P Tyr
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP
response 2
Activated tyrosine- Fully activated receptor
kinase regions tyrosine-kinase Inactive
(unphosphorylated (phosphorylated relay proteins
dimer) dimer)
Figure 11.7

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• Ion channel receptors Signal Gate
Ions
closed
molecule
(ligand)

Ligand-gated Plasma
ion channel receptor Membrane

Gate open

Cellular
response

Gate close

Figure 11.7

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• Concept 11.3: 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

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Signal Transduction Pathways
• At each step in a pathway
– The signal is transduced into a different form,
commonly a conformational change in a
protein

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Protein Phosphorylation and Dephosphorylation
• Many signal pathways
– Include phosphorylation cascades

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• 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

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• A phosphorylation cascade
Signal molecule

Receptor Activated relay 1 A relay molecule


molecule activates protein kinase 1.

Inactive
protein kinase 2 Active protein kinase 1
1 Active transfers a phosphate from ATP
protein to an inactive molecule of
kinase protein kinase 2, thus activating

Ph
1 this second kinase.

os
ph
Inactive

ory
protein kinase ATP

lat
2 ADP Active P 3 Active protein kinase 2

ion
protein then catalyzes the phos-

c
kinase phorylation (and activation) of

as
PP
Pi

c
2 protein kinase 3.

ad
e
Inactive
protein kinase ATP
3 ADP Active P 4 Finally, active protein
protein kinase 3 phosphorylates a
5 Enzymes called protein kinase protein (pink) that brings
phosphatases (PP) PP
Pi 3 about the cell’s response to
catalyze the removal of
the phosphate groups Inactive the signal.
from the proteins, protein ATP
ADP P
making them inactive
Active Cellular
and available for reuse.
protein response
PP
Pi
Figure 11.8
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Small Molecules and Ions as Second Messengers
• Second messengers
– Are small, nonprotein, water-soluble molecules
or ions

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Cyclic AMP
• Cyclic AMP (cAMP)
– Is made from ATP

NH2 NH2 NH2


N N N
N N N
O O N N N N O N N
O
Adenylyl cyclase Phoshodiesterase

O P O P O P O Ch2 HO P O CH2
CH2
O− O− O− O O O O O− O
Pyrophosphate P H2O
P Pi O− O
OH OH OH OH OH
ATP Cyclic AMP AMP

Figure 11.9

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• 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) Adenylyl
G protein cyclase

G-protein-linked GTP
receptor
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

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• Calcium is an important second messenger
– Because cells are able to regulate its
concentration in the cytosol
EXTRACELLULAR Plasma
FLUID membrane
Ca2+
ATP pump
Mitochondrion

Nucleus

CYTOSOL

Ca2+
pump
Endoplasmic
ATP Ca2+ reticulum (ER)
pump

Key High [Ca2+] Low [Ca2+]


Figure 11.11
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• Other second messengers such as inositol
triphosphate and diacylglycerol
– Can trigger an increase in calcium in the cytosol

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1 A signal molecule binds 2 Phospholipase C cleaves a 3 DAG functions as
to a receptor, leading to plasma membrane phospholipid a second messenger
activation of phospholipase C. called PIP2 into DAG and IP3. in other pathways.

EXTRA-
Signal molecule
CELLULAR
(first messenger)
FLUID
G protein

DAG
GTP
G-protein-linked PIP2
receptor Phospholipase C IP3
(second messenger)

IP3-gated
calcium channel

Endoplasmic Various
Cellular
reticulum (ER) Ca 2+ proteins
response
activated
Ca2+
(second
messenger)

4 IP3 quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions
the cytosol and binds to an IP3– the ER (down their con- activate the next
gated calcium channel in the ER centration gradient), raising protein in one or more
Figure 11.12 membrane, causing it to open. the Ca2+ level in the cytosol. signaling pathways.

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• Concept 11.4: Response: Cell signaling leads
to regulation of cytoplasmic activities or
transcription

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Cytoplasmic and Nuclear Responses
• In the cytoplasm
– Signaling pathways regulate a variety of
cellular activities

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• Cytoplasmic response to a signal
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


Active phosphorylase kinase (105)

Inactive glycogen phosphorylase


Active glycogen phosphorylase (106)

Response
Glycogen
Glucose-1-phosphate
(108 molecules)
Figure 11.13
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• 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
factor transcription
Response
factor P
DNA
Gene

NUCLEUS mRNA
Figure 11.14
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Fine-Tuning of the Response
• Signal pathways with multiple steps
– Can amplify the signal and contribute to the
specificity of the response

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Signal Amplification
• Each protein in a signaling pathway
– Amplifies the signal by activating multiple
copies of the next component in the pathway

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The Specificity of Cell Signaling
• The different combinations of proteins in a cell
– Give the cell great specificity in both the
signals it detects and the responses it carries
out

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• Pathway branching and “cross-talk”
– Further help the cell coordinate incoming
Signal

signals molecule

Receptor

Relay
molecules

Response 1 Response Response


Cell A. Pathway leads Cell B. Pathway branches,
2 3
to a single response leading to two responses

Activation
or inhibition

Response 4 Response 5
Cell C. Cross-talk occurs Cell D. Different receptor
Figure 11.15 between two pathways leads to a different response
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Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes
• Scaffolding proteins
– Can increase the signal transduction efficiency
Signal
molecule Plasma
membrane

Receptor

Three
different
protein
Scaffolding kinases
protein

Figure 11.16
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Termination of the Signal
• Signal response is terminated quickly
– By the reversal of ligand binding

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