There are four major transmembrane signalling systems. Ligand-gated channels, G-protein coupled receptors, enzyme-linked receptors and intracellular receptors. Let's start with ligand-gated ion channels. Ligands, usually neurotransmitters such as acetylcholine, cross the neuromuscular junction synaptic cleft to bind to their nicotinic receptors, which are linked to ion channels. Activation of nicotinic receptors induces conformational changes that results in opening of ion channels that allow the influx of various ions, for example, sodium ions which modulate the cellular action potential.
The second type is G-protein coupled receptors. In this type of signalling, binding of the ligand to its extracellular binding site induces conformational change in the transmembrane receptor. This conformational change results in activation of alpha subunit of G protein. Activation of alpha subunit results in dissociation of GDP and binding of GTP to alpha subunit. Binding of GTP to alpha subunit stimulates its dissociation from beta and gamma subunits, which form separate beta-gamma dimer.
Then both alpha subunit and beta-gamma dimer activate various effector targets. For example, alpha subunit activates membrane-bound enzymes such as adenylil cyclase and phospholipase C, which in turn activate a cascade of second messenger reactions, which leads to various biological responses. Thank you.
The third type is enzyme-linked receptors, for example insulin receptors, where binding of insulin to the extracellular domain of the receptors stimulates conformational change that results in phosphorylation and activation of tyrosine kinase enzyme which is part of the intracellular domain. And this is the main difference between enzyme-linked receptors and G-protein coupled receptors, as tyrosine kinase is innate and intrinsic part of the receptor and not detached from from it during activation. Then active phosphorylated tyrosine kinase phosphorylates effector protein called insulin receptor substrate abbreviated as IRS which in turn stimulates a cascade of wild biological responses.
Finally, intracellular receptors. The lipophilic molecules such as steroid hormones pass through cell membrane and bind to and activate their intracellular receptors. The activated internal receptors regulate the expression of various genes.
This video was narrated by Zainab Hamad, a medical student at King's College London.