Cell Signaling

H

ow do cells send signals? Who receives those signals? What response comes about from this communication? Cell signaling is not straightforward, but then again, nothing in physiology ever is. In this article, I’ll try to give you a basic overview of cell signaling, if basic is even a word in this unit!

What is cell signaling?

Cell signaling involves a signaling cell and a target cell. It is when a cell in the body sends out signals which then reach surface receptors on a target cell. These signals – mostly electrical (neural) or chemical (hormonal) – are meant to ultimately generate a response in the cellular machinery of the target cell, causing changes to cellular metabolism, structure, DNA/RNA synthesis, gene expression, lipid formation etc.

Some signals can pass straight through the target cell’s membrane, such as lipid-soluble hormones. These include steroid and thyroid hormones. Once they’ve entered the cell, they will bind to receptors in the cytoplasm of the cell.

Other signals won’t be able to pass straight through and thus, their receptors are located on the cell’s surface. A receptor is a protein which has a signal-specific binding site to which the signal molecule binds. A ligand is the term given to the molecule that fits into the signal-specific binding region of the receptor. Once the signal enters the cell, a response is brought about. But if only it were that simple…

How is the signal sent?

There are a few ways in which a cell can send out a signal: 

• Endocrine signaling
• Neuronal signaling
• Paracrine/Autocrine signaling
• Contact-dependent signaling

Let’s discuss each one…

Endocrine signaling

This involves hormones – chemical signals. An endocrine cell (the signaling cell) releases hormones which travel through blood or interstitial fluid to reach the receptor of a target cell.

This type of signaling works for short or long-distance signal transmissions.

Neuronal signaling

This involves electrical impulses and neurotransmitters. A neuron (the signaling cell) releases neurotransmitters from the axon terminal of the presynaptic neuron. Unlike hormones which travel through blood or ISF, neurotransmitters simply have to jump across a synaptic cleft to reach the receptors on the surface of the postsynaptic neuron. This overall region comprising the pre- and postsynaptic neuron and the gap in between (synaptic cleft) is called the synapse.

This type of signaling also works for short or long-distance transmissions.

Paracrine signaling

This involves signal molecules called local mediators.  The signaling cell releases these molecules into the surrounds which then bind to signal-specific receptors of surrounding target cells.

This type of signaling works for short-distance transmissions only.

Autocrine signaling

This involves signal molecules called local mediators. Unlike paracrine signaling, the signaling cell in autocrine signaling is actually affected by the cells around it, as if a feedback response is inflicted back upon itself. Basically, if the cells around it are not releasing the same signals, the cell experiences weak autocrine signals; however, if the neighbouring cells are releasing identical signals, the cell will experience strong autocrine signals and the response will be stronger. This feedback is facilitated by the fact that the signal molecules released can attach back onto its own receptors - it is its own target cell.

The main difference between paracrine and autocrine signaling is that the signaling cell impacts the surrounding cells in paracrine, whereas it’s vice versa in autocrine.

It’s somewhat like wi-fi receptivity. You wouldn’t get much connectivity the farther away you are from the hotspot, so unsurprisingly, this type of signaling works only for short distances.

Contact-dependent signaling

This involves the signal molecule being already fixed onto the signaling cell’s surface. The cell, with its signal molecule attached, approaches the receptor on the target cell. This contact is how the receptor binds to the signal molecule.

As you can expect, this type of signaling works only for short-distance signal transmissions.

Signaling Cascade

Once the signal is received by the receptor of the target cell, a series of processes occur that involve transforming the signal into a form readable by the target cell (transduction), to ultimately trigger a cellular response.

This series is known as the signaling cascade, and incorporates these processes:

Transfer of the signal (primary messenger) from the signaling cell to the target cell.

Transduction of the signal – converting the signal into a form which the target cell can use (secondary messengers). This is achieved via one of three types of surface receptors…

• Ion-channel-linked receptors
• G-protein-coupled receptors
• Enzyme-coupled receptors

Amplification of the signal using the intracellular signal molecules (secondary messengers).

Integration of the signal with other signals followed by distribution of the signal throughout the cell to enable a range of responses to occur simultaneously.

Modulation factors occur to regulate the response in the cell.

Cell surface receptors

We briefly touched on the three types of surface receptors. These receptors play a role in transduction – converting the receptor-bound signal into a form usable by the target cell. Let’s explain each one…

Ion-channel-linked receptor

This receptor involves an ion channel which opens when a signal molecule attaches to it.

An example is in neuronal signaling when the neurotransmitter acetylcholine binds to the ligand-gated ion channel on the surface of the postsynaptic membrane. The signal molecule is like the key which opens up the gate to let ions move through.

Once the signal molecule e.g. a neurotransmitter binds to the receptor, the ion-channel opens, and ions can be transported in or out of the cell. As a result of ion movement, the membrane potential changes across the membrane.

G-protein-coupled receptor

This receptor involves a G-protein attached to the inner membrane of the target cell. A G-protein is a protein to which a GTP (guanosine triphosphate) or GDP (guanosine diphosphate) molecule can bind, and it has 3 subunits – alpha, beta, and gamma.

A G-protein is inactive when it has a GDP attached. Once the extracellular signal molecule attaches to the protein receptor on the target cell’s surface, the G-protein comes along and binds to this surface receptor. Subsequently, the G-protein lets go of the GDP, and a GTP molecule takes its place. The G-protein is active once the GTP is attached. Finally, the alpha subunit detaches from the beta and gamma subunits.

Something to note about the surface receptor which binds to the G-protein – it has three parts to it:

• The extracellular part that binds to the signal molecule
• The transmembrane part that is like a long-winding tail snaking up and down the surface membrane 7 times.
• The intercellular part that binds to the G-protein

Enzyme-coupled receptor

This receptor involves a surface protein that becomes an active enzyme once a signal molecule binds to the receptor. We know that enzymes are proteins that catalyse (speed-up) reactions, so by activating the enzymatic receptor, it is able to speed-up chemical reactions for processes in the signaling cascade.

I told you, it’s not straightforward – if only cells could just send a phone call or text message like we can. But all this complexity – hormones, neurotransmitters, local mediators, transduction, amplification, ligands, and receptors – can be quite fascinating too. Take it bite by bite, and soon it will all start to make more sense.

See you in my next article Xx

Sources:

Sheehy, P 2019, AVBS2005 Animal Energetics and Homeostasis, lecture: Cell Signaling, lecture PowerPoint slides, The University of Sydney

Sjaastad, ØV, Hove, K & Sand, O 2003, Physiology of Domestic Animals, Scandinavian Veterinary Press, Oslo.