Filopodia powered by class x myosin promote fusion of mammalian myoblasts

eLife

John A Hammer¹  Ernest G Heimsath²  Richard E Cheney²  Michael K Matheny³  Young il Lee³  David W Hammers³  H Lee Sweeney³  Cora C Hart³ 

[1] Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, Bethesda, United States;Department of Cell Biology & Physiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States;Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, United States;University of Florida Myology Institute, Gainesville, United States;

关键词: myogenesis;    myosin x;    filopodia;    satellite cells;    cell fusion;    Human;    Mouse;   

DOI  :  10.7554/eLife.72419

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 multinucleated mammalian muscle formation.

【 授权许可】

CC BY