Drosophila Melted modulates FOXO and TOR activity.
The insulin/PI3K signaling pathway controls both tissue growth and metabolism. Here, we identify Melted as a new modulator of this pathway in Drosophila. Melted interacts with both Tsc1 and FOXO and can recruit these proteins to the cell membrane. We provide evidence that in the melted mutant, TOR activity is reduced and FOXO is activated. The melted mutant condition mimics the effects of nutrient deprivation in a normal animal, producing an animal with 40% less fat than normal.
Teleman
Aurelio A
AA
Chen
Ya-Wen
YW
Cohen
Stephen M
SM
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004789:Enzyme Activation; D051858:Forkhead Transcription Factors; D006801:Humans; D007328:Insulin / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011494:Protein Kinases; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C477334:FOXO protein, Drosophila; C000624650:TSC1 protein, human; C505057:melt protein, Drosophila; C416303:target of rapamycin protein, Drosophila