mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells

• Published in: Biology open 2017-05, Vol.6 (5), p.563-570
• Main Authors: Mensah, Lawrence B, Goberdhan, Deborah C I, Wilson, Clive
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Accumulation; Aging; Akt; AKT protein; Biosynthesis; Diet; Dietary intake; Droplets; Drosophila; Evolution; Food intake; Fruit flies; Growth factors; Homeostasis; Insects; Insulin; Kinases; Lipid metabolism; Lipids; Macromolecules; Metabolism; Mutation; Nurse cells; Nutrients; Obesity; Oogenesis; Phenotypes; Proteins; PTEN protein; Rapamycin; Regulators; Signal transduction; Signaling; TOR protein; Transcription; Triacylglycerol; Tsc1; Tsc2; Tuberous Sclerosis Complex 1; Tuberous Sclerosis Complex 2
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.022210

Insulin and insulin-like growth factor signalling (IIS), which is primarily mediated by the PI3-kinase (PI3K)/PTEN/Akt kinase signalling cassette, is a highly evolutionarily conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth. Previous studies in nutrient-storing germline nurse cells of the ovary showed that a cytoplasmic pool of activated phosphorylated Akt (pAkt) controlled by , an antagonist of IIS, cell-autonomously regulates accumulation of large lipid droplets in these cells at late stages of oogenesis. Here, we show that the large lipid droplet phenotype induced by mutation is strongly suppressed when function is removed. Furthermore, nurse cells lacking either or , which negatively regulate mTORC1 activity, also accumulate large lipid droplets via a mechanism involving , the downstream G-protein target of TSC2, which positively regulates mTORC1. We conclude that elevated IIS/mTORC1 signalling is both necessary and sufficient to induce large lipid droplet formation in late-stage nurse cells, suggesting roles for this pathway in aspects of lipid droplet biogenesis, in addition to control of lipid metabolism.