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Ectopic expression of cone-specific G protein-coupled receptor kinase GRK7 in zebrafish rods leads to lower photosensitivity and altered responses

J. Physiol., 589(Pt 9), 2321-48, 2011

Vision begins with the conversion of photons into electric signals in photoreceptor cells of the retina. Most vertebrates have two types of photoreceptor cells, rods and cones (Figure 1). Rods operate in dim light, and can reliably detect individual photons of light. In contrast, cones function in bright light, and have a less photosensitivity and faster photoresponse kinetics when compared with those of rods. The overall cascade of phototransduction is closely similar, but some proteins are expressed as distinct isoforms between rods and cones. Therefore, it has been thought that many of the differences in physiological response properties arise from differences in the activities and/or expression levels of the transduction proteins. To understand the molecular mechanisms underlying the rod-cone difference in photoresponse, we focused on the G protein-coupled receptor kinase (GRK) responsible for deactivation of visual pigments. Our previous study showed that the Vmax value of major cone GRK, GRK7-1, is 32-fold higher than that of rod GRK, GRK1A in zebrafish (Wada et al. 2006). The finding suggests that the difference in kinase activity between GRK1 in rods and GRK7 in cones contribute to the difference in the photoresponse properties of the cells. To examine this hypothesis, Shiraki and Kojima et al. in Fukada laboratory generated transgenic zebrafish ectopically expressing GRK7-1 in their rods (GRK7-tg), characterized the electrical responses of individual rod photoreceptors in collaboration with Drs. Trevor Lamb and Fivos Vogalis (Australian National University), and examined rod-mediated behaviour in intact animals. In suction electrode recording, exogenous GRK7 in GRK7-tg animals led to lowered rod sensitivity, as occurs in cones (Figure 2). Behavioural measurement of optokinetic responses (OKR) in intact GRK7-tg zebrafish larvae showed that the overall rod visual pathway was less sensitive, in accord with the lowered sensitivity of the rods (Figure 3). These results suggest that the difference in GRK activity is a determinant of rod-cone difference in photosensitivity in rods. Our study establishes the zebrafish expression system as a convenient platform for the investigation of specific components of the phototransduction cascade.