CAMPBELL

BIOLOGY

TENTH
EDITION

Reece Urry Cain Wasserman Minorsky Jackson

11
Cell
Communication

Lecture Presentation by
Nicole Tunbridge and
Kathleen Fitzpatrick
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Cell communication is critical for multicellular organisms!!!!

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Cellular Messaging
Cells can send, receive, interpret and respond
Universal cell signaling mechanisms
Receptor-ligand activation depends on:
type of ligand
receptor presence and #
target cell

Some biological/physiological examples ?????

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The yeast,
Saccharomyces
cerevisiae, is eukaryotic,
single cell

factor

Receptor

1 Exchange
of mating
factors

Yeast cell, a factor

Yeast cell,
mating type a
mating type

2 Mating

3 New a/ cell

a/
Pathway similarities suggest that ancestral signaling molecules that
evolved in prokaryotes and single-celled eukaryotes were adopted for
use in their multicellular descendants
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Local and Long-Distance Signaling

Multicellular organism communicate via signaling
molecules divided into:
Lipophilic

Hydrophilic or lipid-fearing

Animal cells may communicate by

Local
Direct contact - cell-to-cell (synaptic); cell junctions

Autocrine / Paracrine

Long distance
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Figure 11.4

Plasma membranes

Gap junctions
between animal cells
(a) Cell junctions

(b) Cell-cell recognition

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Cell wall

Plasmodesmata
between plant cells

 Animal cells communicate by secreted messenger

molecules that travel only short distances
Autocrine same cell secretes and responds
Positive feedback , ex. T cell activation by cytokines
Paracrine cell secretes and another target cell in local microenviroment
responds
Growth factors (EGF)
Synaptic (neurotransmitters)
in the animal nervous system when a
neurotransmitter is released in response

to an electric signal

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 Endocrine - long-distance signaling; plants and

animals use chemicals called hormones
specialized cells release hormones, which travel to
target cells via the circulatory system
Two classes
Proteins - Insulin (pancreas)

adreneline (adrenal glands)

Steroids estrogen,

Target cell response depends on

presence of specific receptors to that signal

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The Three Stages of Cell Signaling:

A Preview
Earl W. Sutherland discovered how the hormone
epinephrine
Chemical signal is converted to a biochemical signal

Suggested that cells receiving signals went through three

processes
Reception Ligand (hydrophilic and DO NOT enter the
cell) / receptor (transmembrane or integral protein)
Transduction relay molecules

Response change in gene expression, protein

activity, etc..
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Examples that we have discussed?

Figure 11.6-1

EXTRACELLULAR
FLUID
1

Reception

Receptor

Signaling
molecule

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CYTOPLASM
Plasma membrane

Figure 11.6-2

EXTRACELLULAR
FLUID
1

CYTOPLASM
Plasma membrane

Reception

Transduction

Receptor
1

2
Relay molecules

Signaling
molecule

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Figure 11.6-3

EXTRACELLULAR
FLUID
1

CYTOPLASM
Plasma membrane

Reception

Transduction

Response

Receptor
1

2
Relay molecules

Signaling
molecule

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Activation
of cellular
response

Receptor-Ligand Interactions
Types of ligands:
Agonists mimics action of natural ligand
Insulin, erythropoietin, L-dopa

Antagonists competes with natural ligand for

receptor
Tamaxifin (binds estrogen receptor) and Vectibix (antiEGFR antibody) ???

Non-covalent
Receptor expression (# receptors/cell) dictate cell
response
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 There are three main types of membrane

receptors
G protein-coupled receptors

Receptor tyrosine kinases

Ion channel receptors
What are some common characteristics of all 3??

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 G protein-coupled receptors (GPCRs)

Only found in eukaryotes
largest family of cell-surface receptors (>1000 known in humans)
Are the target of 30-50% of all modern medicinal drugs

Ligands range from light-sensitive cmpds, odor, pheromones, hormones

and NTs
Function: growth, pain, taste, immune system, etc
Structure: 7-transmembrane domains: what else??

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 G protein-coupled receptors (GPCRs) are cell

surface transmembrane receptors that work with
the help of a G protein
G proteins bind the energy-rich GTP
G proteins are all very similar in structure

GPCR systems are extremely widespread

(ubiquitous) and diverse in their functions

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Figure 11.8ba

G protein-coupled
receptor

Plasma membrane

GDP

CYTOPLASM

G protein
(inactive)

Enzyme

1
Signaling
molecule

Activated
receptor

GTP
GDP

GDP

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GTP

Inactive
enzyme

Figure 11.8bb

Activated
enzyme

GTP

Cellular
response

GDP
Pi

4
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 2014 Pearson Education, Inc.

 Receptor tyrosine kinases (RTKs) are

membrane receptors that attach phosphates to
tyrosines

A receptor tyrosine kinase can trigger multiple

signal transduction pathways at once
Abnormal functioning of RTKs is associated with
many types of cancers
Why??? Any ideas???

Would you develop a SM or biologic to inhibit a

kinase??
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Figure 11.8ca

Signaling molecule
(ligand)
helix in the

Ligand-binding site

membrane

Tyrosines

CYTOPLASM
1

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Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Receptor tyrosine
kinase proteins
(inactive monomers)

Figure 11.8cb

Signaling molecule

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Dimer

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Figure 11.8cc

Tyr

Tyr

P Tyr

Tyr

Tyr

P Tyr

Tyr P
Tyr P

Tyr

Tyr

P Tyr

Tyr P

ATP

Activated tyrosine
kinase regions
(unphosphorylated
dimer)
3

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6 ADP

Fully activated
receptor tyrosine
kinase (phosphorylated dimer)

Figure 11.8cd

Activated relay
proteins

P Tyr

Tyr P

P Tyr

Tyr P

P Tyr

Tyr P

Inactive
relay proteins
4

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Cellular
response 1
Cellular
response 2

Gated ion Channels

Proteins that are selective for ions when they
change shape
Usually if ligand binds its open; dissociation of
ligand = closed
Allow ions to move that can change electrical
potential = conduction (muscle)

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Figure 11.8d-1

Signaling
molecule
(ligand)

Gate
closed

Ligand-gated
ion channel receptor

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Ions

Plasma
membrane

Figure 11.8d-2

Signaling
molecule
(ligand)

Gate
closed

Ligand-gated
ion channel receptor

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Ions

Plasma
membrane

Gate open

Cellular
response

Figure 11.8d-3

Signaling
molecule
(ligand)

Gate
closed

Ligand-gated
ion channel receptor
3

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Ions

Gate open

Cellular
response

Plasma
membrane

Gate closed

Intracellular Receptors
Intracellular receptor proteins are found in the
cytoplasm or nucleus of target cells
Small or hydrophobic chemical messengers
steroid and thyroid hormones of animals

An activated hormone-receptor complex can act

as a transcription factor (TF), turning on specific
genes

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Figure 11.9

Hormone
(aldosterone)

EXTRACELLULAR
FLUID

Plasma
membrane

Receptor
protein

Hormonereceptor
complex

DNA
mRNA
New
protein

NUCLEUS

CYTOPLASM
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Transduction:
Cascades of molecular interactions relay
signals from receptor to target
Signal transduction usually involves multiple steps
Amplify a signal
Provide more opportunities for coordination and
regulation of the cellular response

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Signal Transduction Pathways

The binding of a signaling molecule to a receptor
triggers the first step in a chain of molecular
interactions

Like falling dominoes the receptor activates another protein,

which activates another, and so on, until the protein

producing the response is activated

At each step, the signal is transduced into a

different form, usually a shape change in a protein
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 2014 Pearson Education, Inc.

Protein Phosphorylation and

Dephosphorylation
Phosphorylation and dephosphorylation of
proteins is a widespread cellular mechanism for
regulating protein activity

Certain amino acids are amendable to

phophorylation (serine, tyrosine)
Protein kinases ??_____________
Many relay molecules in signal transduction
pathways are protein kinases, creating a
phosphorylation cascade
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Figure 11.10a

Signaling molecule

Receptor
Inactive
protein kinase
1

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Activated relay
molecule

Active
protein
kinase
1

Figure 11.10b

Phosphorylation
cascade

Inactive
protein kinase
1

Active
protein
kinase
1
Inactive
protein kinase
2

ATP
ADP

Pi

Active
protein
kinase
2

PP

Inactive
protein kinase
3

ATP
ADP

Pi

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PP

Active
protein
kinase
3

Figure 11.10c

Inactive
protein kinase
3

ATP
ADP

Pi

Active
protein
kinase
3

PP
Inactive
protein

ATP

ADP

PP
i

Regulation???

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Active
protein

Cellular
response

 Protein phosphatases rapidly remove the

phosphates from proteins, a process called
dephosphorylation

This phosphorylation and dephosphorylation is the

molecular switch, turning activities on and off or
up or down, as required

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Small Molecules and Ions as Second

Messengers
Many signaling pathways involve second
messengers
Second messengers are small, nonprotein,
water-soluble molecules or ions that spread
throughout a cell by diffusion
Second messengers participate in pathways
initiated by GPCRs and RTKs
Cyclic AMP and calcium ions are most common
second messengers
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Cyclic AMP
Cyclic AMP (cAMP) is one of the most widely
used second messengers
Adenylyl cyclase, an enzyme in the plasma
membrane, converts ATP to cAMP in response to
an extracellular signal

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Figure 11.11a

Adenylyl cyclase

Pyrophosphate

ATP

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cAMP

Figure 11.11b

Phosphodiesterase

H2O
cAMP

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AMP

 Many signal molecules trigger formation of cAMP

G proteins, G protein-coupled receptors, and
protein kinases
cAMP usually activates protein kinase A, which
phosphorylates various other proteins

Further regulation of cell metabolism is provided by

G-protein systems that
inhibit adenylyl cyclase
inhibit phosphodiesterase (????)
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Figure 11.12

First messenger
(signaling molecule
such as epinephrine)

Adenylyl
cyclase

G protein

GTP

G protein-coupled
receptor

ATP
cAMP

Second
messenger
Protein
kinase A

Cellular responses

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 Role of cAMP in G protein signaling pathways

helps explain how certain microbes cause disease
The cholera bacterium, Vibrio cholerae, produces
a toxin that modifies a G protein - stuck in its
active form
Modified G protein continually makes cAMP,
causing intestinal cells to secrete large amounts of
salt into the intestines
Water follows by osmosis and an untreated person
can soon die from loss of water and salt
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Calcium Ions and Inositol Triphosphate (IP3)

Calcium ions (Ca2+) act as a second messenger in
many pathways
Ca2+ concentration in the cytosol is normally much
lower than the concentration outside the cell
A small change in number of calcium ions thus
represents a relatively large percentage change in
calcium concentration

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Figure 11.13

Endoplasmic
reticulum (ER)

Plasma
membrane
ATP
Mitochondrion

Nucleus

Ca2+
pump
ATP
CYTOSOL ATP
EXTRACELLULAR
FLUID
Key
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High [Ca2+]

Low [Ca2+]

Figure 11.14-1

Signaling molecule
(first messenger)
G protein

EXTRACELLULAR
FLUID

GTP

CYTOSOL

G protein-coupled
receptor

Endoplasmic
reticulum (ER)
lumen

IP3-gated
calcium channel

Ca2+

Nucleus

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DAG
Phospholipase C

PIP2

IP3
(second messenger)

Figure 11.14-2

Signaling molecule
(first messenger)
G protein

EXTRACELLULAR
FLUID

GTP

CYTOSOL

G protein-coupled
receptor

Endoplasmic
reticulum (ER)
lumen

DAG
Phospholipase C

IP3-gated
calcium channel

Ca2+

Nucleus

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Ca2+
(second
messenger)

PIP2

IP3
(second messenger)

Figure 11.14-3

Signaling molecule
(first messenger)
G protein

EXTRACELLULAR
FLUID

GTP

CYTOSOL

G protein-coupled
receptor

Endoplasmic
reticulum (ER)
lumen

DAG
Phospholipase C

IP3-gated
calcium channel

Ca2+

Nucleus

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Ca2+
(second
messenger)

PIP2

IP3
(second messenger)

Various
proteins
activated

Cellular
responses

Nuclear and Cytoplasmic Responses

Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
The response may occur in the cytoplasm or in the
nucleus
Many signaling pathways regulate
the synthesis of enzymes or other proteins,
turning genes on or off in the nucleus
The final activated molecule in the signaling pathway
may function as a transcription factor (TF)
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Figure 11.15a

Growth factor
Receptor

Phosphorylation
cascade

Reception

Transduction

CYTOPLASM
Inactive
transcription
factor

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NUCLEUS

Figure 11.15b

Phosphorylation
cascade

Transduction

CYTOPLASM

Inactive
transcription
factor

Active
transcription
factor
P

Response

DNA
Gene

NUCLEUS
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mRNA

Figure 11.16a

Pathways regulate the activity of enzymes rather

than their synthesis
Reception

Binding of epinephrine to G protein-coupled

receptor
(1 molecule)

Response

Glycogen
Glucose 1-phosphate
(108 molecules)

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Figure 11.16b

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)

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Figure 11.16c

Transduction

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)

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 2014 Pearson Education, Inc.

Regulation of the Response

A response to a signal may not be simply on or
off
There are four aspects of signal regulation to
consider
Amplification of the signal (and thus the response)

Specificity of the response

Overall efficiency of response, enhanced by
scaffolding proteins
Termination of the signal
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The Specificity of Cell Signaling and

Coordination of the Response
Different kinds of cells have different collections of
proteins
Different proteins allow cells to detect and respond
to different signals
The same signal can have different effects in cells
with different proteins and pathways
Pathway branching and cross-talk further help
the cell coordinate incoming signals

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Figure 11.17a

Signaling
molecule

Receptor

Relay
molecules

Response 1

Cell A: Pathway leads

to a single response.
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Response 2

Response 3

Cell B: Pathway
branches, leading to
two responses.

Figure 11.17b

Activation
or inhibition

Response 4

Cell C: Cross-talk
occurs between two
pathways.
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Response 5

Cell D: Different
receptor leads to a
different response.

Scaffolding Proteins and Signaling Complexes

increase efficiency
Scaffolding proteins are large relay proteins to
which other relay proteins are attached
Scaffolding proteins can increase the signal
transduction
group together different proteins involved in the
same pathway
scaffolding proteins may also help activate some of
the relay proteins

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Figure 11.18

Signaling
molecule

Plasma
membrane

Receptor
Three
different
protein
kinases
Scaffolding
protein

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Termination of the Signal

Inactivation mechanisms are an essential aspect
of cell signaling
If ligand concentration falls, fewer receptors will be
bound
Unbound receptors revert to an inactive state

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