Myosin 18 and its role in skeletal muscle: H. Lee Sweeney, P.I. Abstract: This project will investigate the structure and function of an unconventional myosin, myosin XVIII (Myo18). One of the two forms Myo18 expressed in vertebrates, Myo18B, is critical for the generation of sarcomeres in striated muscle. The other form, Myo18A is found in all cells, including muscle, where it may function in other critical cellular processes that require Myo2 filament recruitment and organization, including the early stages of sarcomere formation in striated muscle. Mutations that result in the loss of Myo18B result in myopathies in humans. While Myo18 has been characterized as a non-motor, scaffolding protein, that aids in the assembly of Myo2 filaments, we postulate that it is in fact an active motor protein subject to a novel form of regulation. Only by understanding the design and function of this motor, and using those insights to probe sarcomere formation in muscle cells, will we begin to understand the roles that Myo18 plays in striated muscle and ultimately in other tissues.