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Introduction to cell signaling

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


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.
A sketch of the cell with a caption that says chemical messengers relay the signal. Outside the cell there is a small circle labeled ligand and an arrow from the ligand is pointing toward a structure on the cell membrane labeled receptor. Inside the cell there is an arrow pointing from the receptor towards an unlabeled structure and from the unlabeled structure there is another arrow pointing towards a second unlabeled structure. From the second unlabeled structure inside the cell there is an arrow pointing toward the word 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.

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)6. 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 divide7.
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).

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 pathogens9.
A diagram of two cells with the caption a natural killer, NK, immune cell recognizes a healthy cell of the body by binding to a “self” marker on the cell’s surface. The cell on the left is labeled NK cell and it has a small structure with a circular end extending from the cell membrane. The circular end of the small structure is joined to a receptor on the cell membrane of the cell on the right. The cell on the right is labeled healthy cell.
_Image modified from "Adaptive immune response: Figure 7," by OpenStax College, Biology (CC BY 3.0)._

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