Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38α/β MAPK

Cell Stem Cell. 2012 Oct 5;11(4):541-53. doi: 10.1016/j.stem.2012.05.025.

Abstract

In response to muscle injury, satellite cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal are not understood. We found that satellite cells, once activated, enter the cell cycle and a subset undergoes asymmetric division, renewing the satellite cell pool. Asymmetric localization of the Par complex activates p38α/β MAPK in only one daughter cell, inducing MyoD, which permits cell cycle entry and generates a proliferating myoblast. The absence of p38α/β MAPK signaling in the other daughter cell prevents MyoD induction, renewing the quiescent satellite cell. Thus, satellite cells employ a mechanism to generate distinct daughter cells, coupling the Par complex and p38α/β MAPK signaling to link the response to muscle injury with satellite cell self-renewal.

Publication types

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

MeSH terms

  • Animals
  • Asymmetric Cell Division*
  • Biomarkers / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • Enzyme Activation / genetics
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • MAP Kinase Signaling System
  • Mice
  • Multiprotein Complexes / metabolism
  • Muscle Development
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myogenin / metabolism
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Satellite Cells, Skeletal Muscle / physiology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Isoenzymes
  • Multiprotein Complexes
  • MyoD Protein
  • Myogenin
  • Pard3 protein, mouse
  • Protein Kinase C
  • protein kinase C lambda
  • p38 Mitogen-Activated Protein Kinases