Abstract
Signal transduction in rod cells begins with photon absorption by rhodopsin and leads to the generation of an electrical response. The response profile is determined by the molecular properties of the phototransduction components. To examine how the molecular properties of rhodopsin correlate with the rod-response profile, we have generated a knock-in mouse with rhodopsin replaced by its E122Q mutant, which exhibits properties different from those of wild-type (WT) rhodopsin. Knock-in mouse rods with E122Q rhodopsin exhibited a photosensitivity about 70% of WT. Correspondingly, their single-photon response had an amplitude about 80% of WT, and a rate of decline from peak about 1.3 times of WT. The overall 30% lower photosensitivity of mutant rods can be explained by a lower pigment photosensitivity (0.9) and the smaller single-photon response (0.8). The slower decline of the response, however, did not correlate with the 10-fold shorter lifetime of the meta-II state of E122Q rhodopsin. This shorter lifetime became evident in the recovery phase of rod cells only when arrestin was absent. Simulation analysis of the photoresponse profile indicated that the slower decline and the smaller amplitude of the single-photon response can both be explained by the shift in the meta-I/meta-II equilibrium of E122Q rhodopsin toward meta-I. The difference in meta-III lifetime between WT and E122Q mutant became obvious in the recovery phase of the dark current after moderate photobleaching of rod cells. Thus, the present study clearly reveals how the molecular properties of rhodopsin affect the amplitude, shape, and kinetics of the rod response.
Highlights
The gene knock-out approach has been very useful in addressing this question for the proteins rhodopsin kinase and arrestin [4, 5], this strategy is less appropriate for rhodopsin and G protein, because the deletions of these proteins eliminated the light response [6, 7]
To obtain insight into how the molecular properties of rhodopsin correlate with the photoresponse profile of rod cells, and to elucidate the differences in response properties between rods and cones, we have generated a knock-in mouse line in
Simulation of Rod Photoresponses—The rod-response profile was higher for E122Q rhodopsin compared with WT rhodopwas simulated by the model described previously [29] with sin, at 500 nm the two pigments had very similar extinction some modifications
Summary
To examine how the molecular properties of rhodopsin correlate with the rod-response profile, we have generated a knock-in mouse with rhodopsin replaced by its E122Q mutant, which exhibits properties different from those of wild-type (WT) rhodopsin. To obtain insight into how the molecular properties of rhodopsin correlate with the photoresponse profile of rod cells, and to elucidate the differences in response properties between rods and cones, we have generated a knock-in mouse line in. Our findings reported here clearly show that several of the rhodopsin molecular properties, such as absorption spectrum, photosensitivity, shift in the meta-I/meta-II equilibrium, and meta-III decay, do correlate well with the rodresponse profile and the recovery of rod sensitivity after a bleaching light. The meta-II decay correlates well with the decline phase of the rod response when arrestin is absent
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