Myo10-Driven Filopodia in Skeletal Muscle

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Myo10-Driven Filopodia in Skeletal Muscle: H. Lee Sweeney, P.I. Abstract: This project will investigate the role of an unconventional myosin, myosin X (Myo10), and the filopodia that it generates in myoblasts and nascent myotubles. We postulate that it is only present in muscle cells/satellite cells that are actively in the process of fusing with each other, which would be during muscle growth and regeneration. We further postulate that Myo10 forms filopodia and carries components of the fusion machinery to the tips of those filipodia, greatly increasing the efficiency and probability of cell fusion. We will examine the consequences of loss of Myo10 and its interactions in myogenic cells in the following aims: 1) Delineate the role of myosin X (Myo10) involvement in myoblast fusion and identify regulatory mechanisms of protein targeting and activation in vitro; 2) Evaluate the requirement of myosin X (Myo10) for muscle regeneration; and, 3) Investigate Myosin X (Myo10) as a modifier of chronic muscle disease. These experiments will uncover previously unstudied aspects of the fusion process for skeletal muscle growth and regeneration, and may delineate new modifiers/targets in disease states of skeletal muscle that require rapid muscle regeneration using satellite cells.