Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions.
Studies in Drosophila have characterized insulin receptor/phosphoinositide 3-kinase (Inr/PI3K) signaling as a potent regulator of cell growth, but its function during development has remained uncertain. Here we show that inhibiting Inr/PI3K signaling phenocopies the cellular and organismal effects of starvation, whereas activating this pathway bypasses the nutritional requirement for cell growth, causing starvation sensitivity at the organismal level. Consistent with these findings, studies using a pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion as an indicator for PI3K activity show that PI3K is regulated by the availability of dietary protein in vivo. Hence we surmise that an essential function of insulin/PI3K signaling in Drosophila is to coordinate cellular metabolism with nutritional conditions.
Britton
Jessica S
JS
Molecular and Cellular Biology Program, Seattle, WA 98109, USA.
Lockwood
Wendy K
WK
Li
Ling
L
Cohen
Stephen M
SM
Edgar
Bruce A
BA
D000595:Amino Acid Sequence; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D030801:Animals, Genetically Modified; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004044:Dietary Proteins / Q000378:metabolism / Q000494:pharmacology*; D004330:Drosophila / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D005216:Fat Body / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D005247:Feeding Behavior; D005753:Gastric Mucosa / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013217:Starvation / Q000378:metabolism; D013270:Stomach / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics
D001798:Blood Proteins; D004044:Dietary Proteins; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011972:Receptor, Insulin; C039077:platelet protein P47