Regulators of GPCR Activity: The Arrestins

Abstract

A single photon of light, triggering the physicochemical isomerization of an 11-cis-retinal to its all-trans form, initiates the process of vision. The retinal moiety serves as a tethered ligand for the photoreceptor rhodopsin, a G protein-coupled receptor (GPCR); within milliseconds, the conformational change in rhodopsin that occurs as a result of the retinal isomerization catalyzes guanosine 5′-triphosphate (GTP) for guanosine 5′-diphosphate (GDP) exchange on the heterotrimeric G protein transducin, transducin-dependent activation of a cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE), and the closure of cGMP-gated ion channels. The resulting hyperpolarization of the rod outer segment membrane inhibits release of the neurotransmitter glutamate from the photoreceptor terminal, and the light-induced stimulus is transmitted through the neural network of the retina to the central nervous system (CNS) for processing.