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Published on: August 21, 2014
Regulation of cellular growth by the Drosophila target of rapamycin dTOR
H Zhang1, J P Stallock, J C Ng
1Chiron Corporation, Emeryville, California 94608, USA.
Abstract:
The TOR protein kinases (TOR1 and TOR2 in yeast; mTOR/FRAP/RAFT1 in mammals) promote cellular proliferation in response to nutrients and growth factors, but their role in development is poorly understood. Here, we show that the Drosophila TOR homolog dTOR is required cell autonomously for normal growth and proliferation during larval development, and for increases in cellular growth caused by activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As in mammalian cells, the kinase activity of dTOR is required for growth factor-dependent phosphorylation of p70 S6 kinase (p70(S6K)) in vitro, and we demonstrate that overexpression of p70(S6K) in vivo can rescue dTOR mutant animals to viability. Loss of dTOR also results in cellular phenotypes characteristic of amino acid deprivation, including reduced nucleolar size, lipid vesicle aggregation in the larval fat body, and a cell type-specific pattern of cell cycle arrest that can be bypassed by overexpression of the S-phase regulator cyclin E. Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability.
Insights
The Drosophila TOR (dTOR) protein is essential for larval growth and cell proliferation, responding to nutrients and growth factors. It regulates development by linking growth factor signaling to nutrient availability.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Genetics
Background:
- TOR protein kinases regulate cellular proliferation in response to nutrients and growth factors.
- The precise role of TOR signaling in animal development remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of the Drosophila TOR homolog (dTOR) in larval development.
- To elucidate the mechanisms by which dTOR regulates cell growth and proliferation.
Main Methods:
- Utilized Drosophila melanogaster as a model organism.
- Investigated dTOR's role in cell-autonomous growth and proliferation during larval stages.
- Examined the effects of dTOR loss on cellular phenotypes and cell cycle progression.
Main Results:
- dTOR is cell-autonomously required for normal larval growth and proliferation.
- dTOR activity is necessary for growth factor-induced cellular growth via the PI3K pathway.
- Loss of dTOR leads to phenotypes resembling amino acid deprivation, including cell cycle arrest.
Conclusions:
- dTOR integrates growth factor signaling with nutrient availability to control animal development.
- Phosphorylation of p70 S6 kinase (p70(S6K)) by dTOR is crucial for growth.
- Overexpression of p70(S6K) can rescue dTOR mutant viability, highlighting its importance in development.
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