Drosophilapoly suggests a novel role for the Elongator complex in insulin receptor–target of rapamycin signalling

Abstract

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 describepoly, an essential gene inDrosophilathat mediates InR–TOR signalling. Loss ofpolyresults in lethality at the third instar larval stage, but only after a stage of extreme larval longevity. Analysis inDrosophilademonstrates that Poly and InR interact and thatpolymutants show an overall decrease in InR–TOR signalling, as evidenced by decreased phosphorylation of Akt, S6K and 4E-BP. Metabolism is altered inpolymutants, 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 bothDrosophilaand 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.