A Short Story of GPCR :)

A Short Story of GPCR

GPCR stands for G-protein coupled receptor.

As the name suggests, the receptor which itself is a protein is bound with another protein called G-protein. It is called G-protein because the protein has a bound GDP (Guanidine-di-phosphate).

When a ligand binds to the receptor, conformational change activates the G-protein by exchanging GDP for GTP.

The receptor itself is divided into 3 subunits - α, β, γ. The conformational change results into dissociation of α subunit (bound with GTP). The α subunit is further divided into different types - α_s, α_i, α_q, α_12/13a.

Depending on the α subunit type, the downstream biological signaling differs. The next section briefly talks about the signaling effects depending on the types of α subunit.

G_qα (α₁)- Binding of ligand (eg; NE) to α₁ adrenergic receptor (G_qα) (present mostly in smooth muscles) activates Phospholipase C (PLC). PLC cleaves PIP2 (naturally attached in smooth muscle's inner cell membrane) to IP3 & DAG. IP3 travel to cytoplasm. IP3 activates L-type Ca2+ channels and Ca2+ channels. Increased Ca2+ results in contraction of smooth muscles (intestine, respiratory system). (Note: no SR in smooth muscle).

G_iα (α₂)- It also can be named as α₂ adrenergic receptor and found in the pre synaptic neuron (in all the tissues, so that it can provide negative feedback like a parent to control overactive children). Upon activation G_iα reduce cAMP concentration.

G_sα (β)- activated G_sα ( binds to adenylyl cyclase (AC) to produce the second messenger cAMP by converting ATP to cAMP. This higher concentration of cAMP in the cytoplasm activates the cAMP-dependent protein kinase (also called Protein Kinase A or PKA). Cellular effects of G_sα acting through PKA are described here(link not yet created).

G_qα - Binding of NE to α₁ adrenergic receptor (G_qα) (present mostly in smooth muscles) activates Phospholipase C (PLC). PLC cleaves PIP2 (naturally attached in smooth muscle's inner cell membrane) to IP3 & DAG. IP3 travel to cytoplasm. IP3 activates L-type Ca2+ channels and Ca2+ channels. Increased Ca2+ results in contraction of smooth muscles (intestine, respiratory system). (Note: no SR in smooth muscle)

G_12/13α - function not clear yet.