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Abstract

Skeletal muscle development requires the cell–cell fusion of differentiated myoblasts to form muscle fibers. The actin cytoskeleton is known to be the main driving force for myoblast fusion; however, how actin is organized to direct intercellular fusion remains unclear. Here we show that an actin- and dynamin-2–enriched protrusive structure, the invadosome, is required for the fusion process of myogenesis. Upon differentiation, myoblasts acquire the ability to form invadosomes through isoform switching of a critical invadosome scaffold protein, Tks5. Tks5 directly interacts with and recruits dynamin-2 to the invadosome and regulates its assembly around actin filaments to strengthen the stiffness of dynamin-actin bundles and invadosomes. These findings provide a mechanistic framework for the acquisition of myogenic fusion machinery during myogenesis and reveal a novel structural function for Tks5 and dynamin-2 in organizing actin filaments in the invadosome to drive membrane fusion.

Journal

  • The journal of cell biology

    The journal of cell biology 218(5), 1670-1685, 2019-03

    Rockefeller University Press

Codes

  • NII Article ID (NAID)
    120006714120
  • NII NACSIS-CAT ID (NCID)
    AA00694812
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0021-9525
  • Data Source
    IR 
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