Cell signaling pathways

To make a multicellular organism, cells must be able to communicate with one another, and to do it cells often send out tiny chemical signals that act on the receptors on other cells.

Signals can be classified according to the distance between the signaling cell and the target cell.

Autocrine signals are produced by a cell and go to its own receptors, so the cell sends a signal to itself.

Paracrine signals are produced by a cell and go to target cells that are nearby.

And endocrine signals are produced by a cell and go to target cells that are further away.

Examples of these include hormones that are secreted into the bloodstream, as well as cytokines that can be released at the site of injury and act on the brain to cause a fever.

Signaling molecules or ligands can be hydrophobic, meaning that they tend to repel water, or hydrophilic, meaning that they tend to stay in water.

Hydrophobic signalling molecules can’t freely float in the extracellular space, so they’re brought to the target cells by carrier proteins.

Hydrophobic molecules can diffuse across the cell membrane and bind to receptor proteins inside the target cell - either in the cytoplasm or in the nucleus.

Most signal molecules are hydrophilic, so they can freely float in the extracellular space to reach the target cells, but are then unable to cross the cell membrane.

So to pass on the signal, hydrophilic molecules bind to receptors on the cell surface.

These receptors are transmembrane proteins, with an extracellular end that binds to the ligand, and an intracellular end that triggers a signaling pathway inside the cell.

We can think of the cell signaling pathway in three stages.

The first stage is reception, which is when the target cell’s receptor binds to a ligand. It’s like a key fitting into a lock.

Then there’s transduction, which means that the receptor protein changes in some way and that activates intracellular molecules - the second messengers.

The third stage is the cell’s response to the signal.

Zooming into these transmembrane receptors, there are three major classes: G protein coupled receptors, enzyme-coupled receptors, and ion channel receptors.

G-protein coupled receptors are seven pass transmembrane receptors.

These are really long proteins that have one end that sits outside the cell and binds the ligand, then the snake-like protein dips in and out of the cell membrane seven times, and finally ends on the inside of the cell.

The end of the G-protein coupled receptor that’s within the cell activates intracellular proteins called guanine nucleotide-binding proteins or G proteins.

G proteins are made up of three subunits called alpha, beta, and gamma, sort of like a flower with three petals.

The alpha and the gamma subunits are anchored to the cell membrane and keep the G protein right next to the receptor.

G proteins bind to guanosine diphosphate or GDP when they’re inactive.

When the alpha subunit is bound to GDP, the three subunits stay together, so the flower is closed.

But when the ligand binds, the G-protein coupled receptor changes its shape, and this allows the G protein to release GDP and bind GTP instead, activating the protein.

When the alpha subunit is bound to GTP, the alpha subunit separates from the beta and gamma subunits, like one petal opening and separating from the others.

When that happens, the alpha subunit is free to interact with other proteins - it stimulates some while inhibiting others.

But, to act on other proteins, the alpha subunit turns GTP into GDP, and when that happens the three subunits come together again - the flower closes - and the G protein is turned off.

Overall, there are three types of G proteins: Gq, Gi, and Gs, and each one stimulates and inhibits a different set of enzymes and molecular pathways.

The Gq protein activates the enzyme phospholipase C, which is found in the cell membrane.

Phospholipase C then cleaves a phospholipid called phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate and diacylglycerol.

Inositol trisphosphate is soluble and diffuses freely through the cytoplasm and into the endoplasmic reticulum where it opens up calcium channels.

Since the calcium concentration is higher in the endoplasmic reticulum than in the cytoplasm, calcium flows out of the endoplasmic reticulum to the cytoplasm.