Filopodia powered by class x myosin promote fusion of mammalian myoblasts

• Published in: eLife 2021-09, Vol.10
• Main Authors: Hammers, David W, Hart, Cora C, Matheny, Michael K, Heimsath, Ernest G, Lee, Young Il, Hammer, 3rd, John A, Cheney, Richard E, Sweeney, H Lee
• Format: Article
• Language: English
• Subjects: Animals; Binding sites; Cell Biology; Cell Differentiation; Cell Fusion; Cell Line; Cell Proliferation; Disease Models, Animal; Duchenne's muscular dystrophy; Filopodia; Humans; Mammals; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Mice, Knockout; Microscopy; Muscle Development; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Muscle proteins; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscles; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - pathology; Musculoskeletal system; Myoblasts; Myoblasts, Skeletal - metabolism; Myoblasts, Skeletal - pathology; myogenesis; Myosin; myosin x; Myosins - genetics; Myosins - metabolism; Proteins; Pseudopodia - genetics; Pseudopodia - metabolism; Regeneration; Satellite cells; Satellite Cells, Skeletal Muscle - metabolism; Satellite Cells, Skeletal Muscle - pathology; Skeletal muscle; Stem cell transplantation; Stem cells; Stem Cells and Regenerative Medicine; Time Factors
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.72419

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 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 multinucleated mammalian muscle formation.