The long-term goal of this research program is an integrated understanding of the cellular and molecular mechanisms that govern the development and maintenance of healthy photoreceptors. Here, we propose to investigate two cellular mechanisms essential to photoreceptors at all stages of life, directed membrane traffic and cytoskeletal regulation. These mechanisms are highly conserved in all animals and we will use methods available in Drosophila, an established model system, to extend our understanding of the structure and regulation of the multiprotein complexes that target the photosensory protein, rhodopsin, to the specialized photosensory membrane organelle. ? ? Experiments proposed here build on our demonstration of essential roles for Rab11 and Moesin, key regulators of membrane traffic and cytoskeletal organization, in photoreceptor development. We propose three specific aims to further an understanding of proteins interacting with Rab11 and Moesin and the consequences of their malfunction in developing and adult photoreceptors: 1) We will investigate the role of Rab11 and its associated proteins in rhodopsin transport. 2) We will extend our observation that Arrestin1 is essential for photoreceptor survival. 3) We will continue to investigate the role of Moesin and the specialized membrane-cytoskeletal assembly it organizes at the contact between the photoreceptor's signaling membrane and its cytoplasm. ? ? Insights into the coordination of membrane traffic and the cytoskeleton will be valuable in the rational design of therapies to treat retinal disease and injury. ? ?
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