Receptors and Second Messenger system; G-protein, Enzyme linked and Ligand gated ion channels

There are four major transmembrane signalling systems: Ligand gated channels, G protein coupled receptors, Enzyme linked receptors, and intracellular receptors

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.
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 α subunit of G protein
Activation of α subunit results in dissociation of GDP and binding of GTP to α subunit
Binding of GTP to α subunit stimulates its dissociation from β and γ subunits which form separate βγ dimer
Then both α subunit and βγ dimer activate various effector targets
For example, α subunit activates membrane bound enzymes such as
Adenylyl cyclase and Phospholipase C which in turn
Activate cascade of second messenger reactions
Which leads to various biological responses
Third type is Enzyme linked receptors
For example, insulin receptors
Where binding of insulin to the extracellular domain of the receptors
Stimulate conformational change
That results in phosphorylation and activation of tyrosine kinase enzyme which is part of the intracellular domain
And this 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 it during activation
Then active phosphorylated tyrosine kinase phosphorylates effector protein called
Insulin receptor substrate abbreviated as IRS
Which in turn stimulates cascade of wide 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