DESCRIPTION (provided by applicant): Alterations in the cytoarchitecture of the organ of Corti (OC) cause hearing loss in humans. The regulation of the actin cytoskeleton in epithelial cells of the OC is one of the key elements to understanding the pathogenesis of deafness. But little is known about the mechanism of actin-cytoskeletal modeling especially in supporting cells rather than sensory cells. The unconventional myosin-X (myoX) is an actin-associated motor protein that localizes to supporting cells. The overall hypothesis is that myoX and its binding partners are important regulators of the cytoarchitecture in the OC. The Specific Aims are to: (1) Investigate the developmental expression profiles of myoX in the OC of developing rodents; (2) Investigate the role of the binding proteins in the regulation of dimerization of myoX; and (3) Investigate the role of myoX in regulation of actin dynamics in cultured OC. These goals, to be accomplished by a combination of biochemical and cell biological approaches, will provide new insights into the development of new therapies and prevention of hearing loss.