VISUAL CELL PIGMENT CELL INTERFACE AND DISC TURNOVER

Medical College Of Wisconsin, Milwaukee WI

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Abstract

DESCRIPTION (Applicant's Description): The central idea of this project is that microtubule based motility in photoreceptors is essential for formation and maintenance of the outer segment. The application is based on two new discoveries in my laboratory. First, two cytoplasmic dynein heavy chains are expressed in photoreceptor inner segments and a subset of the dynein localizes to the basal body/cilium complex and outer segment. Second, mammalian homologues of "raft" proteins known to form transport complexes in cilia and flagella are also found associated with the basal body/cilium complex in photoreceptors. We hypothesize that cytoplasmic dynein plays multiple roles in trafficking to support the outer segment. In the cilium and outer segment we propose that cytoplasmic dynein and "raft" proteins are part of a bidirectional transport system similar to "intraflagellar transport" in cilia and flagella and referred to here as "intersegmental transport." Cytoplasmic dynein would serve as a retrograde motor for movement from outer to inner segment while kinesin would serve as an anterograde motor. In the inner segment, we hypothesize that cytoplasmic dynein is critical for the organization of membrane compartments and trafficking to the outer segment. In order to understand the multiple roles of cytoplasmic dynein in photoreceptors we will (1) characterize the molecular form(s) and localization of cytoplasmic dynein, (2) isolate and characterize the protein components of the hypothetical intersegmental rafts, and (3) use targeted expression of transgenes in rod cells in Xenopus to study the function of cytoplasmic dynein and raft proteins in early photoreceptor development.