Drosophila poly suggests a novel role for the Elongator complex in insulin receptor-target of rapamycin signalling.
Multi-cellular organisms need to successfully link cell growth and metabolism to environmental cues during development. Insulin receptor-target of rapamycin (InR-TOR) signalling is a highly conserved pathway that mediates this link. Herein, we describe poly, an essential gene in Drosophila that mediates InR-TOR signalling. Loss of poly results in lethality at the third instar larval stage, but only after a stage of extreme larval longevity. Analysis in Drosophila demonstrates that Poly and InR interact and that poly mutants show an overall decrease in InR-TOR signalling, as evidenced by decreased phosphorylation of Akt, S6K and 4E-BP. Metabolism is altered in poly mutants, as revealed by microarray expression analysis and a decreased triglyceride : protein ratio in mutant animals. Intriguingly, the cellular distribution of Poly is dependent on insulin stimulation in both Drosophila and human cells, moving to the nucleus with insulin treatment, consistent with a role in InR-TOR signalling. Together, these data reveal that Poly is a novel, conserved (from flies to humans) mediator of InR signalling that promotes an increase in cell growth and metabolism. Furthermore, homology to small subunits of Elongator demonstrates a novel, unexpected role for this complex in insulin signalling.
University of Edinburgh , Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Ekin
E
Bolukbasi
Sharron
S
Vass
Neville
N
Cobbe
Bryce
B
Nelson
Victor
V
Simossis
Donald R
DR
Dunbar
Margarete M S
MM
Heck
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006367:HeLa Cells; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D029721:Drosophila Proteins; D012261:Ribonucleoproteins; C552342:poly protein, Drosophila; C094982:InR protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus