MOLECULAR ANALYSIS OF PHOTOTRANSDUCTION

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We are interested in a deeper understanding of the components and regulation of the phototransduction cascade and learning how perturbations in photoreceptor cell physiology lead to various forms of retinal degeneration. We use the Drosophila visual system to examine these broad questions. Drosophila is amenable to molecular, electrophysiological, and genetic approaches to identify molecules and to study in vivo the protein relationships in biochemical pathways. Because many invertebrate visual transduction proteins have vertebrate homologs, both cascades may function in an analogous manner. Thus, the identification of molecules and mechanisms in Drosophila may clarify the vertebrate visual transduction pathway. Many visual transduction molecules exhibit retinal degeneration when altered in either invertebrates or vertebrates. Therefore, studying the role of these molecules in visual transduction will elucidate the mechanisms leading to degeneration. We will extend our analysis of Drosophila retinal degeneration-B (rdgB), which exhibits light-dependent degeneration of photoreceptors. The rdgB protein is a novel phosphatidylinositol transfer protein (PI-TP) required in the visual transduction cascade. One defined role for PI-TPs is regulation of vesicular transport. Immunolocalization of the rdgB protein near the cytosolic face of the rhabdomeres is consistent with the protein functioning in vesicular transport from a trans-Golgi compartment to the rhabdomeres. The rdgB polyclonal antiserum stains vertebrate rod inner segments, suggesting that a vertebrate "photoreceptor" homolog exists. Detailed analysis of the Drosophila molecule and identification of the vertebrate homolog could elucidate aspects of rod outer disc assembly and possibly a novel form of retinal degeneration. The dgq gene encodes two Drosophila photoreceptor-specific G-protein a subunits, DGq1 and DGq2. We demonstrated genetically and biochemically that DGq1 is involved in the light-activated pathway. Further analyses will reveal what is DGq1 's effector molecule and the role of DGq2 in the phototransduction cascade. In addition, an analogous dominant mutation in both DGq1 and transducin leads to an abnormal adaptation response in Drosophila and mouse, respectively. Therefore, further genetic and molecular analyses of DGq1 may elucidate a common adaptation mechanism in both vertebrates and invertebrates.