7

Cell Communication and

Multicellularity
Chapter 7 Key Concepts

7.1 Signals and Signaling Affect Cell

Function
7.2 Receptors Bind Signals to Initiate a
Cellular Response
7.3 The Response to a Signal Spreads
through the Cell
Chapter 7 Key Concepts

7.4 Cells Change in Response to

Signals in Several Ways
7.5 Adjacent Cells in a Multicellular
Organism Can Communicate
Directly
Investigating Life: A Signal for Bonding

In prairie voles, oxytocin and

vasopressin released by brain cells
during mating bind to other brain cells
and trigger life-long bonding and
extensive care of offspring.

Is oxytocin the “trust” signal in humans?

Key Concept 7.1 Focus Your Learning

• Chemical signals that target cells can

be classified according to signal
source and mode of signal delivery.
• A signal transduction pathway
includes a signal, a receptor, and a
response.
• Not all cells respond to a signal,
because some lack the ability to
receive the signal.
7.1 Signals and Signaling Affect Cell Function

All cells process information from the

environment.
The information can be a chemical or a
physical stimulus, such as light.
Signals can come from outside the
organism or from neighboring cells.
7.1 Signals and Signaling Affect Cell Function

Chemical cell signals

• Autocrine signals affect the cells
that made them.
• Juxtacrine signals affect only
adjacent cells.
• Paracrine signals affect nearby
cells.
• Hormones travel to distant cells,
usually via the circulatory system.
Figure 7.1 Chemical Signaling Systems (Part 1)
Figure 7.1 Chemical Signaling Systems (Part 2)
7.1 Signals and Signaling Affect Cell Function

To respond to a signal, a cell must

have a specific receptor that can
detect it.
A signal transduction pathway is the
sequence of events that lead to a
cell’s response to a signal.
7.1 Signals and Signaling Affect Cell Function

A signal transduction pathway involves

a signal, a receptor, and responses.
Responses may involve enzymes and
transcription factors that are activated
or inactivated to bring about the
response.
Figure 7.2 A Signal Transduction Pathway
7.1 Signals and Signaling Affect Cell Function

Crosstalk: Signal transduction

pathways can be interrelated.
• Pathways can branch; one activated
protein may activate multiple
pathways.
• Multiple pathways can converge.
• One pathway may be activated while
another is inhibited.
Key Concepts 7.1 Learning Outcomes

• Use the source and distribution

mechanism of a signal to identify the
type.
• Give an example of how a particular
type of signal (autocrine, juxtacrine,
paracrine, or hormone) functions in an
organism.
Key Concepts 7.1 Learning Outcomes

• Explain how specificity is achieved in

a signal transduction pathway.
• Compare cells found in the same
organism that can and cannot
respond to a specific chemical signal.
Key Concepts 7.2 Focus Your Learning

• Cells make specific receptor proteins

that recognize only the signals to
which they respond.
• Binding of a chemical signal (a ligand)
with its receptor is reversible and is
measured by a dissociation constant.
Key Concepts 7.2 Focus Your Learning

• Intracellular receptors are located

inside the cell, where they interact
with physical signals such as light or
with chemical signals that diffuse
across the cell membrane.
7.2 Receptors Bind Signals to Initiate a Cellular Response

Receptor proteins have very specific

binding sites for chemical signal
molecules, or ligands.
Binding the ligand causes the receptor
protein to change shape.
The binding is reversible and the
ligand is not altered.
Figure 7.3 A Signal and Its Receptor (Part 1)
7.2 Receptors Bind Signals to Initiate a Cellular Response

Receptor (R) binding to its ligand (L) is

reversible:
R + L ↔ RL
KD is the dissociation constant, a
measure of the affinity of the receptor
for its ligand.
The lower the KD, the greater the
affinity.
7.2 Receptors Bind Signals to Initiate a Cellular Response

Some receptors have very low KD

values, which allows them to bind at
very low ligand concentrations.
Many drugs function as ligands.
The KD value of a drug’s binding is
taken into consideration when
determining dosage levels.
7.2 Receptors Bind Signals to Initiate a Cellular Response

Other chemicals similar to ligands can

also bind to receptors.
• Agonists have the same effect as
the ligand.
• Antagonists (inhibitors) bind to the
receptor and prevent the ligand from
binding.
7.2 Receptors Bind Signals to Initiate a Cellular Response

Adenosine (ligand) initiates a signal

transduction pathway in nerve cells
that reduces brain activity.
Caffeine is similar to adenosine and
binds to the same receptors.
Caffeine (antagonist) “ties up” the
adenosine receptors, allowing
continued nerve cell activity.
Figure 7.3 A Signal and Its Receptor (Part 2)
7.2 Receptors Bind Signals to Initiate a Cellular Response

Membrane receptors: Large or polar

ligands (e.g., insulin) bind to cell
membrane receptors.
Intracellular receptors: For small or
nonpolar ligands that can diffuse
across the cell membrane (e.g.,
estrogen).
Figure 7.4 Two Locations for Receptors
7.2 Receptors Bind Signals to Initiate a Cellular Response

Types of cell membrane receptors in

eukaryotes:
• Ion channels
• Protein kinase receptors
• G protein-linked receptors
7.2 Receptors Bind Signals to Initiate a Cellular Response

Ion channel receptors allow ions to

enter or leave a cell.
Signals can be chemical ligands such
as hormones, sensory stimuli such as
light, or electric charge differences.
The acetylcholine receptor on muscle
cells is a gated ion channel.
Figure 7.5 A Gated Ion Channel
7.2 Receptors Bind Signals to Initiate a Cellular Response

Protein kinase receptors catalyze

phosphorylation of themselves and/or
other proteins.
The insulin receptor phosphorylates
itself and other insulin response
substrates, which initiates insertion of
glucose transporters into the cell
membrane.
Figure 7.6 A Protein Kinase Receptor
7.2 Receptors Bind Signals to Initiate a Cellular Response

G protein-linked receptors: Signal

binding to receptor activates a G
protein, which then activates an
effector protein.
G proteins have three subunits. When
activated, one subunit moves through
the cell membrane to an effector
protein.
Figure 7.7 A G Protein-Linked Receptor (Part 1)
Figure 7.7 A G Protein-Linked Receptor (Part 2)
Figure 7.7 A G Protein-Linked Receptor (Part 3)
7.2 Receptors Bind Signals to Initiate a Cellular Response

Intracellular receptors respond to

signals such as light or chemicals
that can cross the cell membrane.
Many are transcription factors. After
binding their ligands, they move to
the nucleus, bind to DNA, and alter
gene expression.
Figure 7.8 An Intracellular Receptor
Key Concepts 7.2 Learning Outcomes

• Explain how and why different cells

respond to different chemical signals.
• Using equations, describe the
chemical kinetics of receptor–ligand
interactions.
• Analyze dissociation constants as a
measure of binding affinity.
• Compare and contrast cell
membrane receptors and intracellular
receptors.
Key Concepts 7.3 Focus Your Learning

• A signal transduction cascade

transmits and amplifies a signal inside
a cell.
• Second–messenger molecules can
transmit and amplify signals within a
cell.
• Signal transduction is regulated in a
cell by various mechanisms.
7.3 The Response to a Signal Spreads through the Cell

Signals sometimes initiate a chain or

cascade of events.
Thus, the initial signal can be amplified
and distributed and result in several
different responses.
7.3 The Response to a Signal Spreads through the Cell

One signal transduction pathway was

worked out using bladder cancer
cells, which have an abnormal form
of G protein called Ras.
The abnormal Ras is permanently
bound to GTP, causing continuous
cell division.
Ras inhibitors stop the cells from
dividing.
Figure 7.9 Signal Transduction and Cancer (Part 1)
Figure 7.9 Signal Transduction and Cancer (Part 2)
7.3 The Response to a Signal Spreads through the Cell

Many cancers have abnormalities in

signal transduction pathways.
By comparing defective and normal
cells, complete signaling pathways
have been worked out.
In a protein kinase cascade one
protein kinase activates the next, and
so on.
Figure 7.10 A Protein Kinase Cascade
7.3 The Response to a Signal Spreads through the Cell

In a protein kinase cascade:

• The signal is amplified at each step.
• Information that arrived at the cell
membrane is communicated to the
nucleus.
• Multiple steps provide specificity.
• Different target proteins provide
variation in the response.
7.3 The Response to a Signal Spreads through the Cell

Some pathways include small

molecules called second
messengers that mediate some
steps.
Cyclic AMP (cAMP) is produced from
ATP by the enzyme adenylyl cyclase.
Figure 7.11 The Formation of Cyclic AMP
7.3 The Response to a Signal Spreads through the Cell

Second messengers serve to amplify

and distribute the signal.
Binding of one signal molecule to a
receptor can lead to production of
many of cAMP.
The cAMP molecules activate many
enzyme targets.
7.3 The Response to a Signal Spreads through the Cell

Second messengers are also involved

in crosstalk.
7.3 The Response to a Signal Spreads through the Cell

Some second messengers are formed

from membrane phospholipids.
Hydrolysis of PIP2 results in two second
messengers: IP3 and DAG.
7.3 The Response to a Signal Spreads through the Cell

IP3 and DAG activate protein kinase C

(PKC).
PKC is a family of protein kinases that
can phosphorylate many proteins,
leading to a variety of cell responses.
7.3 The Response to a Signal Spreads through the Cell

Ca2+ ions can also be second

messengers.
They activate protein kinase C, control
some ion channels, and stimulate
secretion by exocytosis.
7.3 The Response to a Signal Spreads through the Cell

Active transport proteins in cell and ER

membranes pump Ca2+ out of the
cytoplasm, maintaining low
concentrations.
IP3 and other signals open Ca2+
channels and Ca2+ concentrations in
the cytoplasm increase rapidly.
Entry of a sperm into an egg cell also
opens Ca2+ channels.
Figure 7.12 Calcium Ions as Second Messengers
7.3 The Response to a Signal Spreads through the Cell

Nitric oxide (NO) gas is a second

messenger between acetylcholine (a
neurotransmitter) and the relaxation of
smooth muscle in blood vessels,
allowing more blood flow.
Figure 7.13 Nitric Oxide in Signal Transduction (Part 1)
Figure 7.13 Nitric Oxide in Signal Transduction (Part 2)
7.3 The Response to a Signal Spreads through the Cell

Signal transduction is highly regulated.

Concentration of NO is regulated by
how much is made.
Concentration of Ca2+ depends on
activity of membrane pumps and ion
channels.
7.3 The Response to a Signal Spreads through the Cell

Protein kinases, G proteins, and cAMP

are regulated by enzymes that
convert the activated form back to
inactive form.
The balance between enzymes that
activate and enzymes that inactivate
transducers determines the cellular
response to a signal.
Figure 7.14 Regulation of Signal Transduction (Part 1)
Figure 7.14 Regulation of Signal Transduction (Part 2)
Key Concept 7.3 Learning Outcomes

• Describe how a protein cascade

amplifies a signal.
• Explain how the same second-
messenger molecule can be used in
many different signal transduction
pathways.
• Explain how signal transduction
pathways are regulated in a cell.
Key Concept 7.4 Focus Your Learning

• A cell can respond to signals by

opening or closing ion channels.
• A cell can respond to signals by
altering gene transcription.
7.4 Cells Change in Response to Signals in Several Ways

Cells respond to signals by

• Opening ion channels
• Changing enzyme activity
• Differential gene expression
7.4 Cells Change in Response to Signals in Several Ways

Ion channels
• Ion channels can function as signal
receptors.
• The outcome of a signaling pathway
can be the opening of ion channels.
Oxytocin combines these two ion
channel responses.
7.4 Cells Change in Response to Signals in Several Ways

Oxytocin → Receptor → G protein activation →

IP3 signal transduction→ Ca2+ channel opening →
Na+ channel opening
Investigating Life: Is Oxytocin a “Trust” Signal in Humans?

Oxytocin affects prairie vole behavior;

does it work the same way in humans?
Hypothesis: The signal oxytocin is
involved in trust between humans.
Method: Set up an experiment using
pairs of people, measure oxytocin
levels in blood.
Investigating Life: Is Oxytocin a “Trust” Signal in Humans?, Experiment (Part 1)
Investigating Life: Is Oxytocin a “Trust” Signal in Humans?, Experiment (Part 2)
7.4 Cells Change in Response to Signals in Several Ways

Enzymes may be modified in signaling

pathways:
• Phosphorylation by a protein kinase
changes enzyme shape.
• cAMP binds noncovalently to an
enzyme to change its shape.
In both, an active site is exposed, and
the enzyme catalyzes new reactions.
7.4 Cells Change in Response to Signals in Several Ways

In the protein kinase cascade in liver

cells stimulated by epinephrine, two
enzymes are phosphorylated:
1. Glycogen synthase is inhibited—
prevents glucose from being stored as
glycogen.
7.4 Cells Change in Response to Signals in Several Ways

2. Phosphorylase kinase is activated—

stimulates a protein kinase cascade.
 Activation of glycogen
phosphorylase catalyzes breakdown
of glycogen to glucose.
Both events lead to more glucose
available for “flight or fight” response.
7.4 Cells Change in Response to Signals in Several Ways

The signal is amplified in this pathway.

For each molecule of epinephrine that
arrives at the cell membrane, 10,000
molecules of blood glucose result.
Figure 7.15 A Cascade of Reactions Leads to Altered Enzyme Activity
7.4 Cells Change in Response to Signals in Several Ways

Signal transduction is important in gene

expression.
Common targets are transcription
factors, which bind to specific DNA
sequences and activate or inactivate
transcription.
• In the Ras signaling pathway, the
final protein kinase, MAPK, enters the
nucleus and stimulates transcription
of genes for cell division.
Key Concept 7.4 Learning Outcomes

• Describe the signal transduction

pathway stimulated by oxytocin.
• Compare various mechanisms that
cells use to respond to signals.
Key Concept 7.5 Focus Your Learning

• Animal cells can communicate directly

with other cells via gap junctions.
• Development of intercellular
communication was a key step in the
evolution of multicellularity.
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Cells within a tissue communicate

directly via specialized intercellular
junctions
• Gap junctions in animals
• Plasmodesmata in plants
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Gap junctions: Channels between

adjacent cells created by channel
structures called connexons.
Two connexons link, forming a channel
• Cytoplasm can flow through
• Too small for proteins
• Wide enough for ions and small
molecules (e.g., nutrients, hormones,
waste products, second messengers)
Figure 7.16 Communicating Junctions (Part 1)
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Plant cells have plasmodesmata

(tunnels) that traverse the cell walls,
lined by the fused cell membranes.
The desmotubule, derived from the ER,
fills the space in the plasmodesmata
channels.
Figure 7.16 Communicating Junctions (Part 2)
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Plasmodesmata are important for

circulation of materials—similar in
function to capillaries in animals.
Plants rely on rapid diffusion of
hormones through plasmodesmata to
ensure that all cells respond to a signal
at the same time.
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Evolution of multi-cellular organisms

took up to a billion years and probably
occurred in steps.
• Aggregation of cells into a cluster
• Intercellular communication
• Specialization of some cells
• Organization of specialized cells into
tissues
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

The Volvocine line of green algae

illustrates how multicellularity might
have evolved.
Organisms in this line range from single-
celled Chlamydomonas, to clusters of
increasing numbers of cells.
Figure 7.17 Multicellularity
7.5 Adjacent Cells in a Multicellular Organism Can Communicate
Directly

Volvox has 1,000 cells, with somatic and

reproductive cells in separate tissues.
An intercellular signaling mechanism
coordinates the activities of the
separate tissues within the organism.
Key Concept 7.5 Learning Outcomes

• Explain the biological advantages of

gap junctions in animals.
• Design investigations to answer
questions about intercellular
communication.
Investigating Life: A Signal for Bonding

Is oxytocin the “trust” signal in humans?

The experiments showing involvement

of oxytocin in trust opened up a new
field of study called neuroeconomics.
Activities such as massages, hugs, and
sexual activities release oxytocin,
resulting in positive behaviors.