The G protein-coupled receptor kinase GRK1 (rhodopsin kinase) is expressed exclusively in retinal photoreceptors and pinealocytes. In photoreceptors, this enzyme phosphorylates rhodopsin that has been activated by light, leading to the inactivation of phototransduction. Most of what is known regarding photopigment desensitization has been revealed from studies of rod photoreceptors; comparatively little is known about the process of cone pigment phosphorylation and desensitization. We have new evidence that another member of the G protein-coupled receptor kinase family, GRK3, is also expressed in retinal photoreceptors. In contrast to GRK1, GRK3 is expressed at high levels in cones but not rods. Does GRK3 modulate photopic vision through the phosphorylation and desensitization of activated cone photopigments? Does the disruption of GRK3 expression alter the photo- transduction process? The studies outlined in this proposal will address questions and shed new light on a poorly understood aspect of the phototransduction process.
