Species-Specific Differences in Expression of G-Protein-Coupled Receptor Kinase (GRK) 7 and GRK1 in Mammalian Cone Photoreceptor Cells: Implications for Cone Cell Phototransduction

Abstract

Desensitization plays an important role in the rapid termination of G-protein signaling pathways. This process, which involves phosphorylation by a G-protein-coupled receptor kinase (GRK) followed by arrestin binding, has been studied extensively in the rod photoreceptor cell of the mammalian retina. In contrast, less is known regarding desensitization in cone photoreceptor cells, which occurs more rapidly than in rod cells. Recently, our laboratory has cloned a novel GRK family member, GRK7, from the retina of a cone-dominant mammal, the 13-lined ground squirrel. Here we report the cloning of GRK7 from rod-dominant pig and human retinas, suggesting that this kinase plays a role in human visual signaling. Because GRK1 (rhodopsin kinase), the GRK that mediates rhodopsin desensitization in the rod cell, is reportedly expressed in both rods and cones, a detailed comparison of the localization of the two kinases is a necessary step toward determining their potential roles in cone visual signaling. Immunocytochemical analysis using antibodies selective for these two GRKs unexpectedly demonstrated species-specific differences in GRK7 and GRK1 expression in cones. In pigs and dogs, cones express only GRK7, whereas in mice and rats, we detected only GRK1 in cones. These results suggest that either GRK7 or GRK1 may participate in cone opsin desensitization, depending on the expression pattern of the kinases in different species. In contrast, GRK7 and GRK1 are coexpressed in monkey and human cones, suggesting that coordinate regulation of desensitization by both kinases may occur in primates.

Regulation of Mammalian Cone Phototransduction by Recoverin and Rhodopsin Kinase

“…The higher expression and specific activity of GRK7 compared with GRK1 (43) create the potential for much higher rate of pigment phosphorylation in cones compared with rods. In the mouse retina, GRK1 is the only kinase expressed in rods and cones (30). A study with the cone-like photoreceptors in the Nrl Ϫ/Ϫ mouse has demonstrated that mammalian cone opsin is phosphorylated upon light activation (44).…”

The mouse kinome: Discovery and comparative genomics of all mouse protein kinases

“…CYGX is implicated in olfaction (25), and its loss in human parallels that of other olfactory genes. Similarly, the loss in mouse of GPRK7, a potential cone opsin kinase, correlates with the reduced color vision of rodents (26). Cell cycle-related kinases (CDK3 and PLK5) are less likely candidates for gene loss and may indicate redundancy in cell cycle machinery.…”

Phosphorylation of G Protein-coupled Receptor Kinase 1 (GRK1) Is Regulated by Light but Independent of Phototransduction in Rod Photoreceptors

“…Photoreceptors respond to light stimuli within milliseconds and rapidly terminate signaling to recover and maintain their sensitivity under constantly changing ambient light. In rods, G protein-coupled receptor kinase 1 (GRK1) 3 contributes to signal turnoff via phosphorylation of rhodopsin, the G protein-coupled receptor that initiates the phototransduction cascade. Phosphorylation is followed by the binding of arrestin to rhodopsin, which sterically blocks the interaction of rhodopsin with its G protein, transducin (1,2).…”

“…Phosphorylation is followed by the binding of arrestin to rhodopsin, which sterically blocks the interaction of rhodopsin with its G protein, transducin (1,2). GRK1 is expressed in rods of all vertebrates and in cones in several vertebrates (3). For example, GRK1 is expressed in both rods and cones in mice, where it phosphorylates rhodopsin and the cone opsins, respectively (4 -6).…”