Explain what specific signaling information processing happens in the case of GPCR (G protein Coupled Receptors).

Expert Solution

G proteins contain 3 subunits - G-alpha, G-beta, G-gama constitute one of the most important components of cell signalling cascade.

G protein coupled receptor (GPCR) perceive many extracellular signal and transduce them to heterotrimeric G proteins,which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signalling pathway. The signal or primary stimulus could be light ,hormone,odorant, antigen,neurotransmitter or the surface of another cell , through receptor ,transducer, effector.

The another messenger could be cAMP, cGMP, Ca^2+. The triad is responsible for converting the signal from first to second messenger, which could be further regulated by protein kinases or phosphatases in the cytoplasm .

One of the most important signaling cascade is formed by GTP binding proteins or by G proteins ,because of the ability to bind to guanine nucleotide.

General mechanisms are - In the inactive state, G-alpha is bound to G-beta,gama dimer and GDP. G protein mediated signalling starts by binding of an agonist molecule that leads to activation of GPCR. , it is also guanine nucleotide exchange factor that promotes the exchange of GDP/GTP associated with G-alpha sub-unit.

The activated GPCR catalyzes exchange of GTP for GDP on the G-alpha subunit. As a result conformational changes takes place in the GPCR .

The activated G-alpha interacts and regulates many effector molecules such as calcium , potassium channels , adenylyl cyclase PLD , protein kinases , Initially it was hypothesized that the beta-gama dimer acts as a negative regulator and can block activation of adenylyl cyclase by this mechanism.

beta-gama subunit could activate the muscarinic K+ channel and beta-gama subunits positively regulate effectors. Finally the beta-gama subunit shown to be positive regulator of a large number of effectors to the K+ channel , including adenylyl cyclase , phospholipase C-beta , PLA-A_2, , PI3-Kinase and beta - adrenergic receptor kinase.

gladiator answered 2 years ago

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