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Coordinated maintenance of muscle cell size control by AMP-activated protein kinase

Louise Lantier1, Rémi Mounier, Jocelyne Leclerc

  • 1Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 13, 2010
PubMed

Insights

AMP-activated protein kinase (AMPK) normally inhibits muscle cell growth. Lacking AMPK leads to larger muscle cells and increased protein synthesis, revealing AMPK

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Skeletal muscle mass is tightly regulated by signaling pathways controlling protein synthesis and cell proliferation.
  • The mammalian target of rapamycin (mTOR) pathway is a key regulator of muscle growth.
  • AMP-activated protein kinase (AMPK) has been implicated in inhibiting protein synthesis and cell growth.

Purpose of the Study:

  • To investigate the role of AMPK in regulating skeletal muscle cell size.
  • To elucidate the interaction between AMPK and the mTOR/p70S6K signaling pathway in muscle growth.

Main Methods:

  • In vitro studies using AMPK-deficient myotubes.
  • In vivo studies utilizing skeletal muscle-specific AMPKalpha1/alpha2 knockout (KO) mice.
  • Analysis of p70S6K and rpS6 phosphorylation, protein synthesis rates, and myofiber size.

Main Results:

  • AMPK-deficient myotubes exhibited a 1.5-fold increase in size, with elevated p70S6K and rpS6 phosphorylation, indicating enhanced protein synthesis.
  • Rapamycin treatment normalized cell size and p70S6K phosphorylation in AMPK-deficient cells.
  • AMPK-deficient myotubes showed resistance to further size increase induced by MyrAkt, suggesting a critical role for AMPK in hypertrophy.
  • Skeletal muscle-specific AMPKalpha1/alpha2 KO mice displayed increased soleus muscle mass and larger myofibers, associated with heightened p70S6K and rpS6 phosphorylation.

Conclusions:

  • AMPK plays a crucial role in maintaining skeletal muscle cell size control.
  • There is a significant crosstalk between AMPK and mTOR/p70S6K signaling pathways.
  • AMPK acts as a metabolic checkpoint coordinating signals that regulate muscle cell growth.

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