1. Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
- Author
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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), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
- Subjects
Time Factors ,[SDV]Life Sciences [q-bio] ,Urinary incontinence ,mTORC2 ,Mice ,0302 clinical medicine ,Sphincterotomy ,Myocyte ,Cells, Cultured ,0303 health sciences ,Muscles ,TOR Serine-Threonine Kinases ,Homozygote ,Ribosomal Protein S6 Kinases, 70-kDa ,Cell Differentiation ,Urethral pressure ,Muscle atrophy ,Cell biology ,Drug Combinations ,medicine.anatomical_structure ,Proteoglycans ,Collagen ,medicine.symptom ,Plasmids ,Protein Binding ,Signal Transduction ,Genotype ,Genetic Vectors ,Green Fluorescent Proteins ,Immunoblotting ,P70-S6 Kinase 1 ,Biology ,Transfection ,Models, Biological ,Cell Line ,03 medical and health sciences ,Somatomedins ,Notexin ,medicine ,Animals ,Humans ,Muscle, Skeletal ,Protein kinase B ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,RPTOR ,Body Weight ,Skeletal muscle ,Cell Biology ,Mice, Inbred C57BL ,Retroviridae ,Laminin ,Atrophy ,Protein Kinases ,030217 neurology & neurosurgery ,Gene Deletion - 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.
- Published
- 2004
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