Myo10-Driven Filopodia in Skeletal Muscle

骨骼肌中 Myo10 驱动的丝状伪足

基本信息

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
项目类别：
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

项目摘要

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.

骨骼肌中 Myo10 驱动的丝状伪足：H. Lee Sweeney，P.I. 抽象的：该项目将研究非常规肌球蛋白、肌球蛋白 X (Myo10) 的作用及其丝状伪足。产生于成肌细胞和新生肌管中。我们假设它仅存在于肌肉细胞/卫星细胞中它们在肌肉生长和再生过程中积极地相互融合。我们进一步假设 Myo10 形成丝状伪足并将融合机器的组件携带到这些丝状伪足，大大增加了细胞融合的效率和概率。我们将研究后果 Myo10 的丢失及其在生肌细胞中的相互作用，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质靶向和激活的调节机制体外; 2）评估肌肉再生对肌球蛋白X（Myo10）的需求；以及，3) 研究肌球蛋白 X (Myo10) 作为慢性肌肉疾病的调节剂。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，并可能描绘出新的修饰物/目标需要使用卫星细胞快速进行肌肉再生的骨骼肌疾病状态。