The Physiological Roles of Arrestin-1 in Rod Photoreceptor Cells

Abstract

Arrestin-1 is the second most abundant protein in rod photoreceptors and is nearly equimolar to rhodopsin. Its well-recognized role is to "arrest" signaling from light-activated, phosphorylated rhodopsin, a prototypical G protein-coupled receptor. In doing so, arrestin-1 plays a key role in the rapid recovery of the light response. Arrestin-1 exists in a basal conformation that is stabilized by two independent sets of intramolecular interactions. The intramolecular constraints are disrupted by encountering (1) active conformation of the receptor (R*) and (2) receptor-attached phosphates. Requirement for these two events ensures its highly specific high-affinity binding to phosphorylated, light-activated rhodopsin (P-R*). In the dark-adapted state, the basal form is further organized into dimers and tetramers. Emerging data suggest pleiotropic roles of arrestin-1 beyond the functional range of rod cells. These include light-induced arrestin-1 translocation from the inner segment to the outer segment, a process that may be protective against cellular damage incurred by constitutive signaling. Its expanding list of binding partners also hints at additional, yet to be characterized functions. Uncovering these novel roles of arrestin-1 is a subject of future studies.

Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1

“…In the normal mouse retina, bright steady light induces translocation of Arr1 from the inner segments to the outer segments (reviewed in Chen, 2014). In addition, steady light exposure of >1 hr causes a 2-fold increase in Arr1 gene expression, which has been correlated with partial recovery of the rod ERG a-wave, a measure of the rod circulating current (Codega et al, 2009).…”

QR code model: a new possibility for GPCR phosphorylation recognition

“…In the visual system, the homology between arrestin1 and arrestin4 is approximately 58%. Arrestin1 is mainly distributed in rod cells and binds to light-activated phosphorylated rhodopsin, while arrestin4 is only found in cones and has the highest affinity for human green cone opsin [ 91 , 92 ]. Arrestin1 can inactivate both rhodopsin and cone pigment, while arrestin4 can inactivate only cone pigment [ 93 – 95 ].…”