1. Cell Biology
  2. Stem Cells and Regenerative Medicine
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Filopodia powered by class X myosin promote fusion of mammalian myoblasts

  1. David W Hammers
  2. Cora C Hart
  3. Michael K Matheny
  4. Ernest G Heimsath
  5. Young il Lee
  6. John A Hammer III
  7. Richard E Cheney
  8. H Lee Sweeney  Is a corresponding author
  1. University of Florida, United States
  2. University of North Carolina, United States
  3. National Heart, Lung and Blood Institute, United States
  4. University of North Carolina School of Medicine, United States
Research Article
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Cite this article as: eLife 2021;10:e72419 doi: 10.7554/eLife.72419

Abstract

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.

Data availability

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

Author details

  1. David W Hammers

    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2129-4047
  2. Cora C Hart

    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael K Matheny

    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ernest G Heimsath

    Cell Biology & Physiology, University of North Carolina, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Young il Lee

    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. John A Hammer III

    Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2496-5179
  7. Richard E Cheney

    Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6565-7888
  8. H Lee Sweeney

    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States
    For correspondence
    lsweeney@ufl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6290-8853

Funding

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.

Ethics

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.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: July 25, 2021
  2. Accepted: September 13, 2021
  3. Accepted Manuscript published: September 14, 2021 (version 1)

Copyright

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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