Satellite cell-derived TRIM28 is pivotal for mechanical load- and injury-induced myogenesis

EMBO Rep. 2024 Sep;25(9):3812-3841. doi: 10.1038/s44319-024-00227-1. Epub 2024 Aug 14.

Abstract

Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discover that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Interestingly, different from the role reported in a previous study based on C2C12 myoblasts, multiple lines of both in vitro and in vivo evidence reveal that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 are not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discover that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis.

Keywords: Cell Fusion; Hypertrophy; Regeneration; Skeletal Muscle.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Fusion
  • Cell Line
  • Cell Proliferation
  • Humans
  • Mice
  • Muscle Development*
  • Muscle, Skeletal / metabolism
  • Phosphorylation
  • Satellite Cells, Skeletal Muscle* / metabolism
  • Tripartite Motif-Containing Protein 28* / genetics
  • Tripartite Motif-Containing Protein 28* / metabolism

Substances

  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28
  • TRIM28 protein, human