SIGNAL TRANSDUCTION BY G-PROTEINS IN THE RETINAL PE

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The objective of the research set out in this proposal is to gain an understanding of the coordinate physiology of the retinal pigment epithelium (RPE) and the neural retina. Among the many RPE functions critical for the viability of the neural retina is the phagocytosis of packets of shed photoreceptor membranes. The proposed research focuses on the signal transduction processes underlying phagocytosis by the RPE, and is based on the hypothesis that signaling events mediated by Guanine nucleotide-binding proteins (G-proteins) may play a specific role in the interactions between the RPE and photoreceptors. The specific aims are: 1) To identify the G-proteins and G-protein-coupled receptors present in the RPE by cloning and sequencing corresponding cDNAs. 2) To establish the tissue specificity and subcellular localization of the G-proteins and G protein-coupled receptors. 3) To characterize the function of RPE specific proteins and explore their potential roles in the signal transduction processes associated with phagocytosis. The experimental strategy will be based in the techniques of molecular biology, and will make use of the high degree of homology that exists among the G-proteins and among the receptors. Northern analysis, in situ hybridization, and immunocytochemistry will be used to determine tissue specificity and subcellular localization. Assays of ligand binding and phagocytosis will be used to determine the function of RPE specific proteins. This research will contribute to the definition of the signaling potential and cell biology of the RPE on a molecular level. The long term goals are to relate this knowledge to the underlying causes of retinal degeneration, in which the relationship between the RPE and retina is interrupted.