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

Authors :
Lazaro Lorenzo
Athanassia Sotiropoulos
Mickaël Ohanna
Paul A. Kelly
Thomas Lapointe
Emmanuel Petroulakis
Christophe Praud
Nahum Sonenberg
Mario Pende
Andrew K. Sobering
Biologie des Oiseaux et Aviculture (BOA)
Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Fondation pour la recherche médicale
INSERM
Conseil Régional d'Ile-de-France
Association Française contre les Myopathies (9971)
ARC (7647)
Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Source :
Nature Cell Biology, Nature Cell Biology, Nature Publishing Group, 2005, 7 (3), pp.286-294. ⟨10.1038/ncb1231⟩
Publication Year :
2004

Abstract

International audience; 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.

Details

ISSN :
14657392 and 14764679
Volume :
7
Issue :
3
Database :
OpenAIRE
Journal :
Nature cell biology
Accession number :
edsair.doi.dedup.....f5c399b571cfe7507990e7fffea5bdab
Full Text :
https://doi.org/10.1038/ncb1231⟩