Arrestin-1

Arrestin proteins are a family of cell signaling regulators of G protein-coupled receptors. In mammals there are four arrestin isoforms; visual arrestin (s-antigen and arrestin-1) and cone arrestin (arrestin-4) which are largely confined to photoreceptors. β-arrestin 1 (arrestin 2) and β-arrestin-2 (arrestin-3) are ubiquitous and regulate non-visual GPCRs.

Visual arrestin was first discovered as a result of the experimental model of human uveitis, an autoimmune disease of the eye. In this model, called experimental allergic uveitis, animals were injected with extracts made from the retina of the same species mixed with Freund’s complete adjuvant. The animals mounted a strong immune response to the extract, and the antibody response was used to identify several immunogenic retinal proteins. One of these was called S-antigen, for soluble antigen. The protein was found to be abundant in retina, about 48 kDa in molecular weight, and localized in the outer segments of the photoreceptors .

Several years later, Hermann Kühn and colleagues discovered that this protein binds to phosphorylated rhodopsin and prevents this protein from activating transducin. Transducin is a typical heterotrimeric G protein, composed of α and βγ subunits. Rhodopsin phosphorylation is mediated by Rhodopsin kinase (a.k.a. GRK1), the prototypic member of a family of GPCR kinases. Since the S-antigen protein arrested the activity of rhodopsin it was renamed arrestin, and became the prototypic member of the arrestin protein family.