The long-term goal of this project is to understand the function of the actin-based motor, myosin VIIa, in the RPE. Loss of myosin VIIa function results in Usher syndrome type 1B, a combined deafness and blindness disorder. The current application is based on three new developments: (1) Evidence that, in the RPE, myosin VIIa may function in concert with microtubule motors;(2) Discovery of a link between myosin VIIa and the visual cycle;and (3) The establishment of live-cell imaging procedures for the study of RPE organelle transport by molecular motors. We propose to capitalize upon these new findings and developments by: (1) Studying the roles of myosin VIIa and microtubule motors in the transport of melanosomes, phagosomes, and lysosomes in the RPE;(2) Identifying and testing the function of microtubule-binding domain(s) of myosin VIIa;(3) Testing how myosin VIIa affects the visual cycle. The results of these studies will lead to a better understanding of critical cellular processes in the RPE cells, and provide a better basis for testing potential therapies for Usher 1B.
Mutations in the MYO7A gene cause Usher syndrome 1B, a deafness-blindness disorder. The MYO7A protein forms a molecular motor. The proposed research will use state-of-the-art approaches to investigate the function of the MYO7A motor in the RPE. Past work has suggested several roles. These will be tested by imaging the MYO7A motor, together with putative cargo, and microtubule motor proteins with which it may interact. These studies should greatly enhance our understanding of the function of MYO7A, and the underlying cellular basis of retinal defects associated with Usher 1B.
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