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.

Public Health Relevance

Myo10-Driven Filopodia in Skeletal Muscle: H. Lee Sweeney, P.I. Relevance: During skeletal muscle growth and regeneration, satellite cells (muscle stem cells) are activated to divide and fuse with each other and with existing muscle fibers. While key components of the fusion machinery have been identified, we postulate that the molecular motor, myosin X (Myo10), is involved in creating filopodia and delivering components of the fusion machinery to the tips of filipodia in order to optimize the efficiency and rapidity of fusion. As such, it is fundamental to normal skeletal muscle growth and repair and defects in this process may contribute to human muscle disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR075637-01
Application #
9795646
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Boyce, Amanda T
Project Start
2019-07-01
Project End
2024-05-31
Budget Start
2019-07-01
Budget End
2020-05-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Florida
Department
Pharmacology
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611