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Autocrine Signaling

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Autocrine Signaling

Auto- implies that an action is done by someone or something, without help, on its own. Automatic cars are different from manual because they shift gears on their own, without requiring any input from the driver. Autoplay on your favorite streaming service means that the next video will be played without requiring a single click from you. What then is autocrine signaling? It also has the auto- prefix, so that offers us a hint. Read more to discover all about autocrine signaling.

Autocrine signaling definition

Let’s get right to it and define autocrine signaling.

Autocrine signaling is a form of cell communication in which a signal is released by a cell and then acts on that SAME cell, causing some alteration or effect.

Later we will compare and contrast autocrine signaling with another form of cell communication: paracrine signaling, but for now, suffice to say they are different. While they both involve the transmission of a signal to cause an effect, the types of signals they transmit are different and the methods of transmission are especially important in distinguishing one from another.

Autocrine signaling happens to very special kinds of cells with unique capabilities. These cells are called autocrine cells in this context, and the chemical signals they release are called autocrine agents. Autocrine agents from an autocrine cell bind to autocrine receptors on the same autocrine cell (say that five times fast!) The fact that autocrine cells have these receptors on their cell membranes is one of their unique features.

Once the chemical messenger binds to the autocrine receptor, signal transduction occurs.

Signal transduction

Signal transduction can happen in a variety of ways, but it typically involves the following basic steps. Some ligand, in this case, the autocrine agent, binds to a cell surface receptor on the outer layer of the cell membrane of an organism. That binding causes activation of the receptor. The activated receptor, in turn, activates another protein, usually a membrane protein that is close to the receptor. The activated membrane protein then goes on to activate other cytoplasmic proteins, usually one protein activating the next, in tandem. Eventually, the final protein is reached and activated which can then go on to act as any number of things depending on the specific signal. Often, the final protein acts as a transcription factor, going into the nucleus and causing certain genes to be read at either higher or lower rates.

Any of these activated proteins, or even the protein receptor, is likely to undergo a conformational change due to its activation. These conformational (or shape) changes often allow the protein to enact its particular function. Tyrosine kinase receptors are a great example of this.

Multiple RPTKs (receptor protein tyrosine kinases) exist on the surface of a cell, however, when a ligand (the signal) binds to one of them, it causes that receptor to cross-link, or dimerize, with another RTPK in a process known as dimerization.

Dimerization - this is when two molecules (of the same type) join to become a unit comprised of two. It frequently happens with receptor tyrosine kinases.

You may have noticed that the phrase tyrosine kinase ends in an -ase, which we know to be the suffix that implies that the protein we're talking about is an enzyme. This is certainly the case for RPTKs, and when they dimerize, they unlock their enzymatic activity. Each member of the RPTK dimer then adds phosphate (PO3) molecules to several tyrosines on the other RPTK. This is a process known as cross-phosphorylation, where each receptor tyrosine kinase in the dimer phosphorylates the other member of the dimer.

Now phosphorylated, both members of the RPTK are activated, and ready for subsequent proteins (whether membrane proteins or cytoplasmic proteins) to dock, and become activated by them (Fig. 1).

Autocrine signaling receptor tyrosine kinase cusabioFig. 1: Receptor tyrosine kinase activation. Cusabio.

We can see how this example of RPTK follows the general principles of signal transduction. Binding of a ligand leads to activation and conformational change (via dimerization), that in turn causes the activation of subsequent proteins.

Autocrine signaling diagram

A picture is worth a thousand words, they say, but I say why not both? Let's look at a diagram of autocrine signaling in order to consolidate this concept in our minds (Fig. 2).

Autocrine signaling Autocrine signaling diagram Khan AcademyFig. 2: Autocrine signaling diagram. Khan Academy.

First, a ligand is released from within a cell, into the extracellular matrix (same thing as extracellular fluid).

Second, these ligands, known as autocrine agents, land on and bind to the cell surface receptor of an autocrine cell.

Here it is important that we note something: an autocrine cell may be the exact same cell that released the autocrine agent, or it may be a different cell of the same type. This is because all the relevant cells will have the same receptor, and thus will be able to undergo autocrine signaling. For example, if an epithelial cell in your throat releases an autocrine agent, the agent can either bind to the exact cell that released it or any of the millions of other epithelial cells of your throat. Both of these instances would be autocrine signaling.

Third, these ligands cause signal transduction, which we described in detail above.

Lastly, signal transduction causes a particular cellular response.

Autocrine signaling example

A fascinating example of autocrine signaling in medicine and cell biology occurs in the heart. Due to a variety of risk factors including smoking, obesity, and a sedentary lifestyle, the heart's valves (which normally help prevent the backward flow of blood when your heart is trying to push it out to your lungs and your body) can become hardened and stiff. When they are stiff, the heart has to work extra hard and produce higher pressures to force valves to open and close appropriately.

Like with any other muscle, over time, all this hard work causes the heart to get bigger and its muscles to get thicker (You can test this by lifting weights at the gym for a month, and see what all that hard work does to your arms!).

A thick heart is not a good thing, and cardiomyocyte hypertrophy (a fancy term that means enlarged heart muscle) can eventually lead to heart failure or heart attacks. Thus it is not a good thing and is damaging to the cells, typically.

How does all this relate to autocrine signaling? Well, cardiologists (heart doctors) and scientists have discovered an autocrine agent called MIF (macrophage migration inhibitory factor) that acts on cells of the heart during high-pressure states (which occurs with damaged valves as we mentioned). MIF is thought to reduce the heart's ability to hypertrophy, or grow more muscular, which as we know decreases the likelihood of later heart diseases like heart failure and heart attacks. MIF is thus known as a cardioprotective autocrine agent.

Autocrine signaling advantages

What are some advantages of autocrine signaling?

  • They can help to amplify a signal

    • If multiple autocrine cells in the same area are releasing the same autocrine agent.

  • They can help cells orient themselves and sense the presence of other cells in their immediate environment

    • Autocrine cells can utilize the autocrine signaling system as a sort of sensory system, to detect the type and amount of cells in their environment

  • They can be more selective

    • With autocrine signaling, only cells that have the relevant receptors will react to the presence of autocrine agents

  • They are not necessarily exclusive

    • Some autocrine signals also function as paracrine signals in the right circumstances. An example of this is in the Wnt family of proteins.

Autocrine and paracrine signaling

As we mentioned, autocrine and paracrine signals may overlap. In fact, the majority of the cells in our body are capable of both autocrine and paracrine signaling, and many signals can operate in both pathways.

Paracrine signaling - A signal released by a cell that acts on other cells in close proximity to it, we know that both.

Both paracrine and autocrine signals both can act at short distances, and their effects may not last a long time.

Examples of autocrine signaling.

T-cells: White blood cells that kill infected cells of our body. They secrete signals called interleukins, that bind to T-cells themselves, which lead to alterations in the T-cells that make them more specific to the type of cell they are trying to kill.

Cancerous cells: Cancer cells have a problem of over-proliferation and abnormal growth. This is due in part to the signals that they release in the form of growth factors, that promote uncontrollable cell division.

Examples of paracrine signaling

Nitric Oxide: Nitric oxide is released by endothelial cells which act as signaling molecules, causing smooth muscle cells to constrict.

Allergies: WBCs, in response to allergens (triggering molecules that act as signals) can release molecules that cause some of the symptoms of allergies such as flushing, wheezing, rash, etc.

Examples of both paracrine and autocrine signaling.

Natriuretic Peptides: ANP, BNP, and CNP (where NP stands for natriuretic peptides) are proteins produced by the cells of the heart in response to the build-up of blood in the heart (usually due to an inability to pump). All three have been shown to have paracrine and autocrine activity.

Growth Factors: Growth factors like FGF have been shown to have both paracrine and autocrine ability to increase things like bone density and muscle mass.

Autocrine Signaling - Key takeaways

  • Autocrine signaling is a form of cell signaling in which a cell produces a signal for itself, which leads to an effect via signal transduction.
  • Some examples of autocrine signaling include T-cell specification and in unchecked cancer cell growth.
  • Many signals are capable of acting as both paracrine and autocrine signals.
  • Some advantages of autocrine signaling include: the ability to amplify a signal, the ability of a cell to orient itself using a signal, and the ability of a cell to be selective in terms of responses to a signal.

Frequently Asked Questions about Autocrine Signaling

Autocrine signaling is a form of cell signaling in which a cell produces a signal for itself, leading to effect(s).

T-cell specialization

To orient itself to its environment or other cells.

Autocrine signaling has many functions, including orientation, amplification, and selection.

Autocrine signaling is a form of cell signaling in which a cell produces a signal for itself, and it is important because these signals can help to amplify the activity of any one cell

Final Autocrine Signaling Quiz

Question

What is the definition of autocrine signaling?

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Answer

A form of cell communication in which a cell releases a signal which then acts on that same cell, to produce an effect

Show question

Question

In autocrine signaling the signal acts on

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Answer

only the cell that produced it

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Question

What are the types of cell signaling

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Answer

Autocrine, paracrine, endocrine, and synaptic transmission

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Question

What white blood cell uses autocrine signaling to undergo specialization?

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Answer

T cells

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Question

Which disease process uses autocrine signaling to have uncontrolled growth?

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Answer

Cancer 

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Question

Once bound to the receptor, during autocrine signaling, the overall process of relaying a signal is called?

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Answer

Signal transduction

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Question

Receptor tyrosine kinases must first _____ before they can cross-phosphorylate

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Answer

Dimerize

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Question

Many cells in our body are capable of both autocrine and paracrine signaling

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Answer

True

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Question

The most common form of cell signaling is endocrine signaling

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Answer

False

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Question

What is one advantage of autocrine signaling

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Answer

Amplification

Selection

Orientation

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Question

What do bats and autocrine signaling have in common

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Answer

Both release things that help them to orient themselves in their environment

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Question

What is another name for an autocrine signal

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Answer

An autocrine agent

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Question

What does "conformational change" mean

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Answer

Essentially, it is a change in shape; often of a protein

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Question

Fill in the blank: MIF is a cardioprotective autocrine _____

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Answer

Agent / signal

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Question

Which of these is NOT true: 

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Answer

Most cells are capable of paracrine, autocrine, and endocrine signaling

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