Drosophila FoxO regulates organism size and stress resistance through an adenylate cyclase.
Forkhead box class O (FoxO) transcription factors are a family of conserved proteins that regulate the cellular responses to various stimuli, such as energy deprivation, stress, and developmental cues. FoxO proteins are important mediators of the insulin signaling pathway, adjusting growth and metabolism to nutrient availability. Insulin signaling acts together with the glucagon-stimulated cAMP signaling pathway to orchestrate the organism response to various nutritional conditions. In this study, we demonstrate that Drosophila melanogaster FoxO (dFoxO) regulates cAMP signaling by directly inducing the expression of an adenylate cyclase gene, ac76e. Interestingly, ac76e is expressed in a highly restricted pattern throughout fly development, limited to the corpus allatum (CA), gastric cecum, and malpighian tubules. dFoxO activation of AC76E in the CA increases starvation resistance and limits growth. Our results unravel a new role for dFoxO, integrating cAMP and insulin signaling to adapt organism growth to the existing nutritional conditions.
Mattila
Jaakko
J
Department of Molecular Profiling, Merck Research Laboratories, 126 East Lincoln Ave., RY80M-179, Rahway, NJ 07065, USA.
Bremer
Anna
A
Ahonen
Linda
L
Kostiainen
Risto
R
Puig
Oscar
O
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D049628:Body Size; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D005508:Food Deprivation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic
D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases