Drosophila Lipin interacts with insulin and TOR signaling pathways in the control of growth and lipid metabolism.
Lipin proteins have key functions in lipid metabolism, acting as both phosphatidate phosphatases (PAPs) and nuclear regulators of gene expression. We show that the insulin and TORC1 pathways independently control functions of Drosophila Lipin (dLipin). Reduced signaling through the insulin receptor strongly enhanced defects caused by dLipin deficiency in fat body development, whereas reduced signaling through TORC1 led to translocation of dLipin into the nucleus. Reduced expression of dLipin resulted in decreased signaling through the insulin-receptor-controlled PI3K-Akt pathway and increased hemolymph sugar levels. Consistent with this, downregulation of dLipin in fat body cell clones caused a strong growth defect. The PAP but not the nuclear activity of dLipin was required for normal insulin pathway activity. Reduction of other enzymes of the glycerol-3 phosphate pathway affected insulin pathway activity in a similar manner, suggesting an effect that is mediated by one or more metabolites associated with the pathway. Taken together, our data show that dLipin is subject to intricate control by the insulin and TORC1 pathways, and that the cellular status of dLipin impacts how fat body cells respond to signals relayed through the PI3K-Akt pathway.
Department of Biological Sciences, SCEN 601, 1 University of Arkansas, Fayetteville, AR 72701, USA.
Sandra
S
Schmitt
Department of Biological Sciences, SCEN 601, 1 University of Arkansas, Fayetteville, AR 72701, USA.
Rupali
R
Ugrankar
Department of Biological Sciences, SCEN 601, 1 University of Arkansas, Fayetteville, AR 72701, USA.
Stephanie E
SE
Greene
Department of Biological Sciences, SCEN 601, 1 University of Arkansas, Fayetteville, AR 72701, USA.
Meenakshi
M
Prajapati
Department of Biological Sciences, SCEN 601, 1 University of Arkansas, Fayetteville, AR 72701, USA mlehmann@uark.edu.
Michael
M
Lehmann
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D050356:Lipid Metabolism / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C558497:Lpin protein, Drosophila
Insulin signaling; Lipin; TOR signaling