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