Photoreceptor outer segment membranes, the site of initial photon capture initiating phototransduction, undergo renewal with total replacement occurring at ten-day intervals throughout life. A challenge to cellular integrity concerns the post biosynthetic delivery of replacement proteins from the inner to the outer segment over the photoreceptor lifetime. Complex trafficking pathways require multiple components, e.g., UNC119 acyl-binding proteins, small GTPases such as ARL3, and GAP proteins like RP2. Mutations in UNC119 and RP2 are associated with cone-rod dystrophy and X-linked retinitis pigmentosa, respectively. This application will: i) identify pathways for transducin transport in rods, particularly after light-induced translocation; and ii) generate knockout models for NPHP10 and devise gene replacement therapies for NPHP5 and NPHP10 LCA.
NIH ExPorter
NIH ExPorter