Functional Comparison of Rod and Cone Gαt on the Regulation of Light Sensitivity

The signaling cascades mediated byGprotein-coupled receptors (GPCRs) exhibit a wide spectrum of spatial and temporal response properties to fulfill diverse physiological demands. However, the mechanisms that shape the signaling response of the GPCR are not well understood. In this study, we replaced cone transducin alpha (cT alpha) for rod transducin alpha (rT alpha) in rod photoreceptors of transgenic mice, which also express S opsin, to evaluate the role of G alpha subtype on signal amplification from different GPCRs in the same cell; such analysis may explain functional differences between retinal rod and cone photoreceptors. We showed that ectopically expressed cT alpha 1) forms a heterotrimeric complex with rod G beta(1)gamma(1), 2) substitutes equally for rT alpha in generating photoresponses initiated by either rhodopsin or S-cone opsin, and 3) exhibited similar light-activated translocation as endogenous rT alpha in rods and endogenous cT alpha in cones. Thus, rT alpha and cT alpha appear functionally interchangeable. Interestingly, light sensitivity appeared to correlate with the concentration of cT alpha when expression is reduced below 35% of normal. However, quantification of endogenous cT alpha concentration in cones showed a higher level to rT alpha in rods. Thus, reduced sensitivity in cones cannot be explained by reduced coupling efficiency between the GPCR and G protein or a lower concentration of G protein in cones versus rods.