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First published online July 31, 2003
doi: 10.1242/10.1242/jcs.00661
Research Article |
1 Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University
of California, Los Angeles, CA 90095-1489, USA
2 Department of Microbiology, Immunology and Molecular Genetics, Jonsson
Comprehensive Cancer Center, University of California, Los Angeles, CA
90095-1489, USA
3 Department of Molecular, Cell and Developmental Biology, Jonsson Comprehensive
Cancer Center, University of California, Los Angeles, CA 90095-1489, USA
Authors for correspondence (e-mail:
jlengyel{at}ucla.edu;
fuyut{at}microbio.ucla.edu)
Accepted 8 May 2003
Precise body and organ sizes in the adult animal are ensured by a range of signaling pathways. In a screen to identify genes affecting hindgut morphogenesis in Drosophila, we identified a P-element insertion in dRheb, a novel, highly conserved member of the Ras superfamily of G-proteins. Overexpression of dRheb in the developing fly (using the GAL4:UAS system) causes dramatic overgrowth of multiple tissues: in the wing, this is due to an increase in cell size; in cultured cells, dRheb overexpression results in accumulation of cells in S phase and an increase in cell size. Using a loss-of-function mutation we show that dRheb is required in the whole organism for viability (growth) and for the growth of individual cells. Inhibition of dRheb activity in cultured cells results in their arrest in G1 and a reduction in size. These data demonstrate that dRheb is required for both cell growth (increase in mass) and cell cycle progression; one explanation for this dual role would be that dRheb promotes cell cycle progression by affecting cell growth. Consistent with this interpretation, we find that flies with reduced dRheb activity are hypersensitive to rapamycin, an inhibitor of the growth regulator TOR. In cultured cells, the effect of overexpressing dRheb was blocked by the addition of rapamycin. These results imply that dRheb is involved in TOR signaling.
Key words: Cell cycle, Growth, Drosophila, Rheb, TOR
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