Myo10-Driven Filopodia in Skeletal Muscle

骨骼肌中由Myo10驱动的丝状足：H.Lee Sweeney，P.I. 摘要： 这个项目将研究一种非传统的肌球蛋白，肌球蛋白X(Myo10)的作用，以及它的丝状伪足。 在成肌细胞和新生肌小管中产生。我们推测它只存在于肌肉细胞/卫星细胞中。 它们活跃在相互融合的过程中，这将是肌肉生长和再生的过程。 我们进一步假设Myo10形成丝状足，并将融合机制的组件携带到 这些丝状孢子，极大地提高了细胞融合的效率和概率。我们将研究其后果 Myo10的缺失及其在肌源性细胞中的相互作用的研究目的如下：1)描述肌球蛋白X的作用 (Myo10)参与成肌细胞融合并确定蛋白靶向和激活的调节机制 在体外；2)评估肌球蛋白X(Myo10)对肌肉再生的需求；以及3)研究肌球蛋白X (Myo10)作为慢性肌肉疾病的修饰物。这些实验将揭示以前没有研究过的方面。 骨骼肌生长和再生的融合过程，并可能描绘出新的修饰物/靶点 骨骼肌的疾病状态，需要使用卫星细胞快速肌肉再生。

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.