Filopodia powered by class X myosin promote fusion of mammalian myoblasts
Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. In mice, conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided
Article and author information
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR075637)
- H Lee Sweeney
National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54-AR-052646)
- H Lee Sweeney
Fondation Leducq (13CVD04)
- H Lee Sweeney
Muscular Dystrophy Association (MDA549004)
- David W Hammers
National Institute of General Medical Sciences (R01-GM134531)
- Richard E Cheney
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Florida. Protocol #201910602.
- Pekka Lappalainen, University of Helsinki, Finland
- Received: July 25, 2021
- Preprint posted: July 28, 2021 (view preprint)
- Accepted: September 13, 2021
- Accepted Manuscript published: September 14, 2021 (version 1)
- Version of Record published: October 8, 2021 (version 2)
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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