c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration

PLoS One. 2013 Nov 19;8(11):e81757. doi: 10.1371/journal.pone.0081757. eCollection 2013.

Abstract

Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Animals
  • Cell Differentiation
  • Cell Fusion
  • Cell Movement
  • Cytoskeleton / chemistry
  • Cytoskeleton / metabolism
  • Embryo, Mammalian
  • Embryonic Development / genetics
  • Female
  • Gene Expression
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle Cells / cytology
  • Muscle Cells / metabolism*
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / metabolism*
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Pseudopodia / metabolism
  • Regeneration / genetics*

Substances

  • Proto-Oncogene Proteins c-met