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

Mickaël Ohanna, Andrew K. Sobering, Thomas Lapointe, Lazaro Lorenzo, Christophe Praud, Emmanuel Petroulakis, Nahum Sonenberg, Paul A. Kelly, Athanassia Sotiropoulos, Mario Pende

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

Abstract

The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps of muscle development and growth, but the physiological relevance and the downstream effectors are under investigation. Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin. In the differentiated state, S6K1-/- myotubes have a normal number of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires distinct effectors for the control of muscle cell cycle and size, potentially opening new avenues of therapeutic intervention against neoplasia or muscle atrophy.

Original languageEnglish (US)
Pages (from-to)286-294
Number of pages9
JournalNature Cell Biology
Volume7
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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