Atrophy of S6K1(−/−) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
Open accessAbstract
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.
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Impairment of mTORC1 activity or its downstream target p70S6K1 impinges muscle mass.
“When mTORC1 activity [89] or the activity of its down stream target p70S6K1 [92,93] are impaired then muscle mass is impinged.”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [93]
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- Authors
- Ohanna, M., Sobering, A. K., Lapointe, T., Lorenzo, L., Praud, C., Petroulakis, E., Sonenberg, N., Kelly, P. A., Sotiropoulos, A., & Pende, M.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- McGill University (CA)
- Corresponding author
- Sotiropoulos, Athanassia
- Pende, Mario
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2005-02-20
- Volume
- 7
- Issue
- 3
- Pages
- 286-294
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1998763810
- Cited by
- 392
- References
- 27
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 23 · 2016: 21 · 2015: 16 · 2014: 23 · 2013: 23 · 2012: 33
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Novartis Foundation
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- S6 kinase 1, mTOR, skeletal muscle atrophy, myoblast proliferation, cell cycle regulation, Akt signaling, insulin-like growth factor I, rapamycin, muscle hypertrophy
- MeSH terms
- Animals, Atrophy, Body Weight, Cell Differentiation, Cell Line, Cells, Cultured, Collagen, Drug Combinations, Genetic Vectors, Genotype, Homozygote, Humans, Laminin, Mice, Inbred C57BL, Models, Biological, Muscles, Plasmids, Protein Binding, Protein Kinases, Proteoglycans, Retroviridae, Somatomedins, Time Factors, Transfection, Immunoblotting, Signal Transduction, Gene Deletion, Muscle, Skeletal, Ribosomal Protein S6 Kinases, 70-kDa, Green Fluorescent Proteins, Mice, TOR Serine-Threonine Kinases
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