The long term goal of this research is to define the molecular basis of visual signaling in mammalian cone photoreceptors.
Specific aims are to examine potential mechanistic differences in function of three selected cone signaling components compared to those in rods: the cone visual pigments, the cone cGMP phosphodiesterase, and the cone guanylyl cyclases. The visual pigments will be examined for their bleaching profile, activation of transducins, and interactions with arrestins. The cGMP phosphodiesterase will be assessed for intrinsic activity, non-catalytic cGMP control of activity, and G-protein control of activation and shut- off. The guanylyl cyclases will be examined for differences in intrinsic activity and mechanisms that regulate enzymatic activity. Biochemical mechanisms are sought that might explain why mammalian cones are less sensitive, hyperpolarize more rapidly with smaller amplitudes, and adapt over a larger range of light fluence with little change in signal shape in comparison with rod responses.
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