G protein-coupled receptor adaptation mechanisms.
G protein-coupled receptors (GPCRs) transduce extracellular signals that modulate the activity of a wide variety of biological processes, such as neurotransmission, chemoattraction, cardiac function, olfaction, and vision. However, GPCR signalling desensitizes rapidly as the consequence of receptor phosphorylation. G protein-coupled receptor kinase-mediated receptor phosphorylation promotes the binding of beta-arrestin proteins, which not only uncouple GPCRs from their cognate heterotrimeric G protein, but also target them for endocytosis. The sequestration (endocytosis) of desensitized GPCRs to endosomes is required for their dephosphorylation and subsequent resensitization to their pre-ligand exposed state. This review concentrates on the mechanisms underlying GPCR desensitization and resensitization.
Ferguson
S S
SS
John P. Robarts Research Institute, London, Ontario, Canada.
Caron
M G
MG
D000222:Adaptation, Physiological; D000818:Animals; D019390:Arrestins / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*
D019390:Arrestins; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins