Transduction &Signaling in Retinal Photoreceptors

Johns Hopkins University, Baltimore MD

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Abstract

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to understand in detail the phototransduction mechanisms in retinal rods and cones and in other vertebrate photoreceptors. The specific aims are: 1) to understand why cones are much less sensitive to light than rods, and have response kinetics several-fold faster. We shall focus on cone pigments, particularly their tendency to dissociate into the apoprotein and 11-cis retinal (without isomerization), and its tendency to isomerize thermally at a high rate to the active state. 2) to continue study of phototransduction in the lizard parietal-eye photoreceptor. In particular, we would like to understand the chromatic antagonism in this cell, in which green light activates a cGMP-activated channel, while blue light closes the channel, acting through opposite effects on the cGMP-phosphodiesterase. We propose to characterize the detailed physiology and the biochemical/molecular aspects of this antagonism. The hope is to use this unusual system to shed new light on the G-protein control of the cGMP-phosphodiesterase. 3) to study the assembly of the rod and cone cyclic nucleotide-activated channels. In particular, we shall examine in detail a domain on the alpha-subunits of these channels identified by us that appears to be involved in channel assembly. We shall also examine whether this domain has to do with the selective assembly of the alpha- and beta-subunits of these channels into hetero-oligomers in rods and cones instead of perfectly functional alpha-homomeric channels. The methodology involves a combination of electrophysiology, molecular biology and biochemistry.