Introduction to cell signaling

Learn how cells communicate with one another using different kinds of short-
and long-range signaling in our bodies.

Introduction
Think your cells are just simple building blocks, unconscious
and static as bricks in a wall? If so, think again! 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!

In this article, we'll examine the basic principles of how cells

communicate with one another. We'll first look at how cell-
cell signaling works, then consider different kinds of short-
and long-range signaling that happen in our bodies.

Overview of cell signaling

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. There, they can
float – like messages in a bottle – over to neighboring cells.

Sending cell: this cell secretes a ligand.

Target cell: this cell has a receptor that can bind the ligand. The ligand
binds to the receptor and triggers a signaling cascade inside the cell,
leading to a response.

Nontarget cell: this cell does not have a receptor for the ligand (though
it may have other kinds of receptors). The cell does not perceive the
ligand and thus does not respond to it.

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, a
general term for molecules that bind specifically to other
molecules (such as receptors).

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.
You can learn more about how this works in the articles
on ligands and receptors, signal relay, and cellular responses.

Forms of signaling
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.

Paracrine signaling
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.
[Example: spinal cord development]

Synaptic signaling
One unique example of paracrine signaling is synaptic
signaling, in which nerve cells transmit signals. This process
is named for the synapse, the junction between two nerve
cells where signal transmission occurs.

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).
 Synaptic signaling. Neurotransmitter is released from vesicles at the
end of the axon of the sending cell. It diffuses across the small gap
between sending and target neurons and binds to receptors on the
target neuron.
Image modified from "Signaling molecules and cellular receptors: Figure 2," by
OpenStax College, Biology (CC BY 3.0).

The neurotransmitters that are released into the chemical

synapse are quickly degraded or taken back up by the
sending cell. This "resets" the system so they synapse is
prepared to respond quickly to the next signal.
 Paracrine signaling: a cell targets a nearby cell (one not attached by
gap junctions). The image shows a signaling molecule produced by one
cell diffusing a short distance to a neighboring cell.

Autocrine signaling: a cell targets itself, releasing a signal that can bind
to receptors on its own surface.
Image modified from "Signaling molecules and cellular receptors: Figure 1," by
OpenStax College, Biology (CC BY 3.0).

Autocrine signaling
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). This may seem like an odd thing for a cell to do, but
autocrine signaling plays an important role in many
processes.

For instance, 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.

Endocrine signaling
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.

In humans, endocrine glands that release hormones include

the thyroid, the hypothalamus, and the pituitary, as well as
the gonads (testes and ovaries) and the pancreas. Each
endocrine gland releases one or more types of hormones,
many of which are master regulators of development and
physiology.

For example, the pituitary releases growth hormone (GH),

which promotes growth, particularly of the skeleton and
cartilage. Like most hormones, GH affects many different
types of cells throughout the body. However, cartilage cells
provide one example of how GH functions: it binds to
receptors on the surface of these cells and encourages them
to divide.

Endocrine signaling: a cell targets a distant cell through the

bloodstream. A signaling molecule is released by one cell, then travels
 through the bloodstream to bind to receptors on a distant target cell
elsewhere in the body.
Image modified from "Signaling molecules and cellular receptors: Figure 2," by
OpenStax College, Biology (CC BY 3.0).

[Do plants have endocrine signaling?]

Signaling through cell-cell contact

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 and ions are able to move between
cells, but large molecules like proteins and DNA cannot fit
through the channels without special assistance.

The transfer of signaling molecules transmits the current

state of one cell to its neighbor. This allows a group of cells to
coordinate their response to a signal that only one of them
may have received. In plants, there are plasmodesmata
between almost all cells, making the entire plant into one
giant network.

Signaling across gap junctions. A cell targets a neighboring cell

connected via gap junctions. Signals travel from one cell to the other
by passing through the gap junctions.
Image modified from "Signaling molecules and cellular receptors: Figure 1," by
OpenStax College, Biology (CC BY 3.0).

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.

_Image modified from "Adaptive immune response: Figure 7," by OpenStax College,
Biology (CC BY 3.0)._