Cell Communication

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 Overview: The Cellular Internet

• Cell-to-cell communication is essential for

multicellular organisms
• Biologists have discovered some universal
mechanisms of cellular regulation

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

 Local and Long-Distance Signaling

• Cells in a multicellular organisms communicate by

chemical messengers
• Animal and plant cells have cell junctions that
directly connect the cytoplasm of adjacent cells
• In local signaling, animal cells may communicate
by direct contact
• In many other cases, animal cells communicate
using local regulators, messenger molecules that
travel only short distances
• In long-distance signaling, plants and animals use
chemicals called hormones
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-3
Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells
Cell junctions

Cell-cell recognition
LE 11-4

Local signaling Long-distance signaling

Target cell Electrical signal Endocrine cell Blood

along nerve cell vessel
triggers release of
neurotransmitter

Neurotransmitter
Secreting Secretory diffuses across
cell vesicle synapse Hormone travels
in bloodstream
to target cells

Local regulator
diffuses through Target cell Target
extracellular fluid is stimulated cell

Paracrine signaling Synaptic signaling

Hormonal signaling
 The Three Stages of Cell Signaling: A Preview

• Earl W. Sutherland discovered how the hormone

epinephrine acts on cells
• Sutherland suggested that cells receiving signals
went through three processes:
– Reception

– Transduction

– Response

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

LE 11-5_3

EXTRACELLULAR CYTOPLASM
FLUID
Plasma membrane

Reception Transduction Response

Receptor

Activation
of cellular
response
Relay molecules in a signal transduction
pathway

Signal
molecule
 Concept 11.2: Reception: A signal molecule binds
to a receptor protein, causing it to change shape
• The binding between a signal molecule (ligand)
and receptor is highly specific
• A conformational change in a receptor is often the
initial transduction of the signal
• Most signal receptors are plasma membrane
proteins

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

 Intracellular Receptors

• Some receptor proteins are intracellular, found in

the cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers can
readily cross the membrane and activate
receptors
• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals
• An activated hormone-receptor complex can act
as a transcription factor, turning on specific genes

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

LE 11-6
Hormone EXTRACELLULAR
(testosterone) FLUID The steroid
hormone testosterone
passes through the
plasma membrane.

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

The hormone-
receptor complex
enters the nucleus
and binds to specific
genes.
DNA

mRNA The bound protein

stimulates the
transcription of
the gene into mRNA.
NUCLEUS New protein

The mRNA is
translated into a
specific protein.
CYTOPLASM
 Receptors in the Plasma Membrane

• Most water-soluble signal molecules bind to

specific sites on receptor proteins in the plasma
membrane
• There are three main types of membrane
receptors:
– G-protein-linked receptors

– Receptor tyrosine kinases

– Ion channel receptors

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

• A G-protein-linked receptor is a plasma membrane
receptor that works with the help of a G protein
• The G-protein acts as an on/off switch: If GDP is
bound to the G protein, the G protein is inactive

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

LE 11-7aa

Signal-binding site

Segment that
interacts with
G proteins

G-protein-linked receptor
• Receptor tyrosine kinases are membrane
receptors that attach phosphates to tyrosines
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• A kinase, alternatively known as a
phosphotransferase, is a type of enzyme that
transfers phosphate groups from high-energy
donor molecules, such as ATP, to specific
substrates. The process is referred to as
phosphorylation.

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

LE 11-7b

Signal Signal-binding site

molecule
 Helix in the Signal
membrane molecule

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

Receptor tyrosine
kinase proteins Dimer
CYTOPLASM (inactive monomers)

Activated relay
proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P P Tyr Tyr P
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
(unphosphorylated (phosphorylated Inactive
dimer) dimer) relay proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• An ion channel receptor acts as a gate when the
receptor changes shape
• When a signal molecule binds as a ligand to the
receptor, the gate allows specific ions, such as
Na+ or Ca2+, through a channel in the receptor

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

LE 11-7c
Signal Gate
molecule closed Ions
(ligand)

Plasma
Ligand-gated
membrane
ion channel receptor

Gate open

Cellular
response

Gate closed
 Concept 11.3: Transduction: Cascades of molecular interactions
relay signals from receptors to target molecules in the cell

• Transduction usually involves multiple steps

• Multistep pathways can amplify a signal: A few

molecules can produce a large cellular response
• Multistep pathways provide more opportunities for
coordination and regulation

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

 Signal Transduction Pathways

• The molecules that relay a signal from receptor to

response are mostly proteins
• 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 conformational change

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

 Protein Phosphorylation and Dephosphorylation

• In many pathways, the signal is transmitted by a

cascade of protein phosphorylations
• Phosphatase enzymes remove the phosphates

• This phosphorylation (kinases) and

dephosphorylation (phosphotases) system acts as
a molecular switch, turning activities on and off

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

LE 11-8
Signal molecule

Receptor
Activated relay
molecule

Inactive
protein kinase
1 Active
protein
kinase
1

Ph
Inactive

o
sp
protein kinase ATP

ho
2 ADP Active P

ry
la
protein

ti o
kinase

n
PP

ca
Pi 2

sc
ad
Inactive

e
protein kinase ATP
ADP Active P
3
protein
PP kinase
Pi 3

Inactive
protein ATP
ADP P
Active Cellular
PP protein response
Pi
 Small Molecules and Ions as Second Messengers

• Second messengers are small, nonprotein, water-

soluble molecules or ions
• The extracellular signal molecule that binds to the
membrane is a pathway’s “first messenger”
• Second messengers can readily spread
throughout cells by diffusion
• Second messengers participate in pathways
initiated by G-protein-linked receptors and
receptor tyrosine kinases

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

 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

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

LE 11-9

Adenylyl cyclase Phosphodiesterase

Pyrophosphate H2O
P Pi

ATP Cyclic AMP AMP

• Many signal molecules trigger formation of cAMP

• Other components of cAMP pathways are G

proteins, G-protein-linked 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

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

LE 11-10

First messenger
(signal molecule
such as epinephrine)
Adenylyl
G protein cyclase

G-protein-linked GTP
receptor

ATP
Second
cAMP messenger

Protein
kinase A

Cellular responses
 Calcium ions and Inositol Triphosphate (IP3)

• Calcium ions (Ca2+) act as a second messenger in

many pathways
• Calcium is an important second messenger
because cells can regulate its concentration

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

LE 11-11
EXTRACELLULAR
FLUID Plasma
membrane

Ca2+
pump
ATP
Mitochondrion

Nucleus

CYTOSOL

Ca2+
pump

Endoplasmic
reticulum (ER)
ATP Ca2+
pump

Key High [Ca2+] Low [Ca2+]

• A signal relayed by a signal transduction pathway
may trigger an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve
inositol triphosphate (IP3) and diacylglycerol (DAG)
as second messengers

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

LE 11-12_3
EXTRACELLULAR Signal molecule
FLUID (first messenger)

G protein

DAG
GTP

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

IP3-gated
calcium channel

Various Cellular
Endoplasmic Ca2+ proteins re-
reticulum (ER) activated sponses
Ca2+
(second
CYTOSOL messenger)
 Cytoplasmic and Nuclear Responses

• Ultimately, a signal transduction pathway leads to

regulation of one or more cellular activities
• The response may occur in the cytoplasm or may
involve action in the nucleus
• Many pathways regulate the activity of enzymes

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

LE 11-13
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)
• Many other signaling pathways regulate the
synthesis of enzymes or other proteins, usually by
turning genes on or off in the nucleus
• The final activated molecule may function as a
transcription factor

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

LE 11-14
Growth factor
Reception
Receptor

Phosphorylation
cascade
Transduction

CYTOPLASM

Inactive
transcription Active
factor transcription
factor Response
P

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 © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

 Signal Amplification

• Enzyme cascades amplify the cell’s response

• At each step, the number of activated products is

much greater than in the preceding step

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

 The Specificity of Cell Signaling

• Different kinds of cells have different collections of

proteins
• These differences in proteins give each kind of cell
specificity in detecting and responding to signals
• The response of a cell to a signal depends on the
cell’s particular collection of proteins
• Pathway branching and “cross-talk” further help
the cell coordinate incoming signals

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

LE 11-15
Signal
molecule

Receptor

Relay
molecules

Response 1 Response 2 Response 3

Cell A. Pathway leads Cell B. Pathway branches,

to a single response leading to two 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
 Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes

• Scaffolding proteins are large relay proteins to

which other relay proteins are attached
• Scaffolding proteins can increase the signal
transduction efficiency

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

LE 11-16

Signal Plasma
molecule membrane

Receptor

Three
different
protein
kinases

Scaffolding
protein
 Termination of the Signal

• Inactivation mechanisms are an essential aspect

of cell signaling
• When signal molecules leave the receptor, the
receptor reverts to its inactive state

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