Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control

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Updated: Aug 19, 2026

Isolation and Differentiation of Primary Myoblasts from Mouse Skeletal Muscle Explants
06:53

Isolation and Differentiation of Primary Myoblasts from Mouse Skeletal Muscle Explants

Published on: October 15, 2019

Mickaël Ohanna1, Andrew K Sobering, Thomas Lapointe

  • 1Inserm, Avenir, U584, Université Paris 5, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, Paris, F-75730, France.

Nature Cell Biology
|February 22, 2005
PubMed

Insights

S6 kinase 1 (S6K1) is crucial for muscle cell size regulation by mTOR and Akt. Its absence reduces muscle cell size without affecting proliferation, highlighting distinct pathways for cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Physiology

Background:

  • Mammalian target of rapamycin (mTOR) and Akt proteins are key regulators of muscle development and growth.
  • The specific downstream effectors and physiological relevance of these pathways are still under investigation.

Purpose of the Study:

  • To investigate the role of S6 kinase 1 (S6K1) as a downstream effector of mTOR and Akt in muscle cell growth.
  • To determine the physiological significance of S6K1 in controlling muscle cytoplasmic volume and hypertrophy.

Main Methods:

  • Utilized genetic deletion of S6K1 in mice to study its effects on myoblast proliferation and size.
  • Administered rapamycin to inhibit mTOR and compared the effects with S6K1 deletion.
  • Assessed the hypertrophic response of S6K1-deficient myotubes to insulin-like growth factor 1 (IGF1), nutrients, and Akt activation.

Main Results:

  • S6K1 deletion significantly reduced myoblast size, similar to mTOR inhibition by rapamycin, but did not affect cell proliferation.
  • S6K1-deficient myotubes exhibited reduced size and blunted hypertrophic responses to IGF1, nutrients, and Akt.
  • These findings indicate that mTOR utilizes distinct effectors for regulating muscle cell cycle versus cell size.

Conclusions:

  • S6K1 is an essential mediator for Akt and mTOR in controlling muscle cell cytoplasmic volume.
  • The study reveals distinct molecular mechanisms governing muscle cell proliferation and growth.
  • These findings may offer new therapeutic strategies for conditions like neoplasia and muscle atrophy.

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