Myo10-Driven Filopodia in Skeletal Muscle

骨骼肌中 Myo10 驱动的丝状伪足

• 批准号: 10634534
• 负责人: H Lee Sweeney
• 金额: $ 37.6万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634534
• 关键词: Actins; Acute; Age; Blood Vessels; Breathing; Cell Culture Techniques; Cell Nucleus; Cell fusion; Cells; Characteristics; Chimeric Proteins; Chronic; Data; Defect; Development; Direct Lytic Factors; Disease; Duchenne muscular dystrophy; Female; Fiber; Filopodia; Freezing; Genetic; Growth; Human; In Vitro; Injury; Knock-out; Laboratories; Locomotion; Mammals; Modeling; Molecular Motors; Motor; Movement; Mus; Muscle; Muscle Cells; Muscle Development; Muscle Fibers; Muscle satellite cell; Myoblasts; Myopathy; Myosin ATPase; Natural regeneration; Nature; Neoplasm Metastasis; Phenotype; Physiological; Play; Probability; Process; Proteins; Regulation; Role; Sarcomeres; Skeletal Muscle; Skeleton; Tissues; experimental study; in vivo; in vivo regeneration; insight; male; muscle regeneration; neural; postnatal; regeneration following injury; repaired; satellite cell; skeletal muscle growth; stem cells; transmission process

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.

骨骼肌Myo 10驱动的丝状伪足：H.李·斯威尼私家侦探 摘要： 该项目将研究一种非传统的肌球蛋白，肌球蛋白X（Myo 10）的作用，以及它 在成肌细胞和新生肌管中产生。我们假设它只存在于肌肉细胞/卫星细胞中 在肌肉生长和再生的过程中，它们会活跃地相互融合。 我们进一步假设Myo 10形成丝状伪足，并将融合机器的组件携带到细胞的尖端。 这些丝状体，大大提高了细胞融合的效率和概率。我们将研究 Myo 10的缺失及其在肌原细胞中的相互作用，目的如下：1）阐明肌球蛋白X的作用 （Myo 10）参与成肌细胞融合，并确定蛋白质靶向和激活的调控机制 体外; 2）评价肌球蛋白X（Myo 10）对肌肉再生的需求; 3）研究肌球蛋白X （Myo 10）作为慢性肌肉疾病的修饰剂。这些实验将揭示以前未研究的方面 骨骼肌生长和再生的融合过程，并可能描绘新的修饰剂/靶点， 骨骼肌的疾病状态，需要使用卫星细胞进行快速肌肉再生。