Regulation of cellular growth by the Drosophila target of rapamycin dTOR.
By Hongbing Zhang, J. Stallock, Joyce Ng, C. Reinhard, T. P. Neufeld. Genes & Development, 2000
656 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/ada5a2516bd87f413b13dc6d615f2d0dbbca8e2c
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cell Biology
In Molecular Biology
Citations in the corpus
- Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “In flies, deletion of dTOR mimics amino acid withdrawal by inhibiting larval growth and causing the accumulation of lipid vesicles in the larval fat body that reflects the breakdown and mobilization of stored nutrients (Britton and Edgar, 1998; Oldham et al., 2000; Zhang et al., 2000).”
- Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. (2002, background): “Indeed, modulation of Drosophila TOR (dTOR) and its downstream targets, ribosomal protein S6 kinase (dS6K) and eukaryotic initiation factor 4E-binding protein (d4EBP), produce cell size phenotypes (Montagne et al. 1999; Oldham et al. 2000; Zhang et al. 2000; Miron et al. 2001).”
- Role and regulation of starvation-induced autophagy in the Drosophila fat body. (2004, background): “D) TEM images of fat body cells from wild-type animals that2003; Zhang et al., 2000), and to cause a marked reducwere well fed (A) or starved of dietary protein by incubating in 20%tion in fat body cell size (Butterworth et al., 1965). sucrose for 3 hr (B–”
- Upstream and downstream of mTOR. (2004, background): “Cells deficient in both dPTEN and dTOR display a phenotype similar to that of cells deficient in dTOR alone, indicating that dTOR is epistatic to dPTEN and acts downstream of PI3K (Oldham et al. 2000; Zhang et al. 2000).”
- Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development (2013, background): “As previously reported (25), we found that wildtype larvae grown on food containing rapamycin show a delay in larval development.”
- Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks (2011, background): “Drosophila mutants deficient in dTOR exhibit reduced cell and body size (85, 120), as well as a massive accumulation of autophagic vesicles in the fat body even under fed conditions (92).”
- Regulation of translation initiation by FRAP/mTOR. (2001, background): “Interestingly, dTOR mutant cell clones generated by FLP/FRT-mediated mitotic recombination exhibit a pronounced decrease in cell size in several adult tissues, and in the developing wing imaginal disc (Zhang et al. 2000).”