Cell Communications
J. Sam Johnson, [Link]., [Link]., Ph.D.,
No cell can live in isolation, must interact with
environment
In multicellular organisms, cells must
communicate with each other
Growth involves intricate signaling
Same with Differentiatio n
Even Metabolism requires signaling
Earl W. Sutherland, discovered how hormone
epinephrine acts on cells, suggested that
cells receiving signals went t h r o u g h t h r e e
p ro cesses:
◦ Reception of signal
◦ Transduction of signal
◦ Response to signal
Stages in Cell Signaling
EXTRACELLULAR
FLUID
Reception Transduction CYTOPLASM Response
Plasma membrane
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signal
molecule
Cells can detect what's going on around
them, and they can respond in real time to
cues from their neighbors and environment.
At this very moment, your cells are sending
and receiving millions of messages in the
form of chemical signaling molecules!
Cells typically communicate using chemical
signals.
These chemical signals, which are proteins or
other molecules produced by a sending cell, are
often secreted from the cell and released into the
extracellular space.
Not all cells can “hear” a particular chemical
message.
In order to detect a signal (that is, to be a target
cell), a neighbor cell must have the right receptor
for that signal.
When a signaling molecule binds to its receptor, it
alters the shape or activity of the receptor,
triggering a change inside of the cell.
Signaling molecules are often called ligands.
The message carried by a ligand is often relayed
through a chain of chemical messengers inside the
cell.
Ultimately, it leads to a change in the cell, such as
alteration in the activity of a gene or even the
induction of a whole process, such as cell division.
Thus, the original intercellular (between-cells) signal
is converted into an intracellular (within-cell) signal
that triggers a response.
Cell-cell signaling involves the transmission of a signal
from a sending cell to a receiving cell.
However, not all sending and receiving cells are next-
door neighbors, nor do all cell pairs exchange signals
in the same way.
There are four basic categories of chemical signaling
found in multicellular organisms:
◦ Paracrine signaling,
◦ Autocrine signaling,
◦ Endocrine signaling, and
◦ Signaling by direct contact.
The main difference between the different categories
of signaling is the distance that the signal travels
through the organism to reach the target cell.
Often, cells that are near one another
communicate through the release of chemical
messengers (ligands that can diffuse through the
space between the cells).
This type of signaling, in which cells
communicate over relatively short distances, is
known as paracrine signaling.
Paracrine signaling allows cells to locally
coordinate activities with their neighbors.
Although they're used in many different tissues
and contexts, paracrine signals are especially
important during development, when they allow
one group of cells to tell a neighboring group of
cells what cellular identity to take on
One unique example of paracrine signaling
is synaptic signaling, in which nerve cells
transmit signals.
When the sending neuron fires, an electrical
impulse moves rapidly through the cell, traveling
down a long, fiber-like extension called an axon.
When the impulse reaches the synapse, it triggers
the release of ligands called neurotransmitters,
which quickly cross the small gap between the
nerve cells.
When the neurotransmitters arrive at the
receiving cell, they bind to receptors and cause a
chemical change inside of the cell (often, opening
ion channels and changing the electrical potential
across the membrane).
In autocrine signaling, a cell signals to itself,
releasing a ligand that binds to receptors on its own
surface (or, depending on the type of signal, to
receptors inside of the cell).
Autocrine signaling is important during development,
helping cells take on and reinforce their correct
identities. From a medical standpoint, autocrine
signaling is important in cancer and is thought to
play a key role in metastasis (the spread of cancer
from its original site to other parts of the body).
In many cases, a signal may have both autocrine and
paracrine effects, binding to the sending cell as well
as other similar cells in the area.
When cells need to transmit signals over long
distances, they often use the circulatory system
as a distribution network for the messages they
send.
In long-distance endocrine signaling, signals are
produced by specialized cells and released into
the bloodstream, which carries them to target
cells in distant parts of the body.
Signals that are produced in one part of the body
and travel through the circulation to reach far-
away targets are known as hormones.
Gap junctions in animals and plasmodesmata in
plants are tiny channels that directly connect
neighboring cells.
These water-filled channels allow small signaling
molecules, called intracellular mediators, to
diffuse between the two cells.
Small molecules, such as calcium ions are able to
move between cells, but large molecules like
proteins and DNA cannot fit through the
channels without special assistance.
In another form of direct signaling, two cells
may bind to one another because they carry
complementary proteins on their surfaces.
When the proteins bind to one another, this
interaction changes the shape of one or both
proteins, transmitting a signal.
This kind of signaling is especially important
in the immune system, where immune cells
use cell-surface markers to recognize “self”
cells (the body's own cells) and cells infected
by pathogens.
A cell junction (or intercellular bridge) is a type of
structure that exists within the tissue of
some multicellular organisms, such as animals.
Cell junctions consist of multiprotein
complexes that provide contact between
neighboring cells or between a cell and
the extracellular matrix.
They also build up the paracellular barrier of
epithelia and control the paracellular transport.
Cell junctions are especially abundant
in epithelial tissues.
Cell junctions are especially important in
enabling communication between
neighboring cells via specialized proteins
called communicating junctions.
Cell junctions are also important in reducing
stress placed upon cells.
Combined with cell adhesion
molecules and extracellular matrix, cell
junctions help hold animal cells together.
In vertebrates, there are three major types of
cell junction:
◦ Adherens junctions, desmosomes and
hemidesmosomes (anchoring junctions)
◦ Gap junctions (communicating junction)
◦ Tight junctions (occluding junctions)
Adherens Junction - joins actin bundles
between cells.
Desmosome - joins intermediate filaments
between cells.
Hemi-desmosome - anchors cell
intermediate filaments to ECM
Gap Junction - cell-cell communication
(signaling), passage of small molecules.
Tight Junction - seals neighbouring cells.
The chains of molecules that relay signals
inside a cell are known as intracellular signal
transduction pathways.
When a ligand binds to a cell-surface
receptor, the receptor’s intracellular domain
(part inside the cell) changes in some way.
Generally, it takes on a new shape, which may
make it active as an enzyme or let it bind
other molecules.
The change in the receptor sets off a series of
signaling events.
For instance, the receptor may turn on
another signaling molecule inside of the cell,
which in turn activates its own target.
This chain reaction can eventually lead to a
change in the cell's behavior or
characteristics.
Proteins can be activated or inactivated in a
variety of ways.
However, one of the most common tricks for
altering protein activity is the addition of a
phosphate group to one or more sites on the
protein, a process called phosphorylation.
In general, phosphorylation isn’t permanent. To
flip proteins back into their non-phosphorylated
state, cells have enzymes called phosphatases,
which remove a phosphate group from their
targets.
Although proteins are important in signal
transduction pathways, other types of molecules
can participate as well.
Many pathways involve second messengers,
small, non-protein molecules that pass along a
signal initiated by the binding of a ligand (the
“first messenger”) to its receptor.
Second messengers include
◦ Ca2+ ions
◦ Cyclic AMP (cAMP), a derivative of ATP
◦ Inositol phosphates, which are made from
phospholipids.
Signaling pathways share a common goal: to
produce some kind of cellular response.
◦ Gene Expression
◦ Growth
◦ Cellular Metabolism
◦ Apoptosis
