Actomyosin contractility scales with myoblast elongation and enhances differentiation through YAP nuclear export

Sci Rep. 2019 Oct 29;9(1):15565. doi: 10.1038/s41598-019-52129-1.

Abstract

Skeletal muscle fibers are formed by the fusion of mononucleated myoblasts into long linear myotubes, which differentiate and reorganize into multinucleated myofibers that assemble in bundles to form skeletal muscles. This fundamental process requires the elongation of myoblasts into a bipolar shape, although a complete understanding of the mechanisms governing skeletal muscle fusion is lacking. To address this question, we consider cell aspect ratio, actomyosin contractility and the Hippo pathway member YAP as potential regulators of the fusion of myoblasts into myotubes. Using fibronectin micropatterns of different geometries and traction force microscopy, we investigated how myoblast elongation affects actomyosin contractility. Our findings indicate that cell elongation enhances actomyosin contractility in myoblasts, which regulate their actin network to their spreading area. Interestingly, we found that the contractility of cell pairs increased after their fusion and raise on elongated morphologies. Furthermore, our findings indicate that myoblast elongation modulates nuclear orientation and triggers cytoplasmic localization of YAP, increasing evidence that YAP is a key regulator of mechanotransduction in myoblasts. Taken together, our findings support a mechanical model where actomyosin contractility scales with myoblast elongation and enhances the differentiation of myoblasts into myotubes through YAP nuclear export.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actomyosin / genetics*
  • Actomyosin / metabolism
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Cycle Proteins / genetics*
  • Cell Differentiation / physiology
  • Cell Nucleus / genetics
  • Cell Shape / genetics
  • Cell Size
  • Fibronectins / genetics
  • Hippo Signaling Pathway
  • Mice
  • Muscle Contraction / genetics
  • Muscle Fibers, Skeletal / metabolism*
  • Myoblasts / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Signal Transduction / genetics
  • YAP-Signaling Proteins

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Fibronectins
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Actomyosin
  • Protein Serine-Threonine Kinases