title: mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation inDrosophilaovarian nurse cells.
abstract: 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 theDrosophilaovary showed that a cytoplasmic pool of activated phosphorylated Akt (pAkt) controlled byPten, 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 byPtenmutation is strongly suppressed whenmTorfunction is removed. Furthermore, nurse cells lacking eitherTsc1orTsc2, which negatively regulate mTORC1 activity, also accumulate large lipid droplets via a mechanism involvingRheb, 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.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK lbmensah@mit.edu.|The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
authors.forename: Lawrence B
authors.identifier: http://orcid.org/0000-0001-5793-1891
authors.initials: LB
authors.lastname: Mensah
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Deborah C I
authors.initials: DCI
authors.lastname: Goberdhan
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Wilson
keywords: Akt; Insulin; Obesity; Triacylglycerol; Tsc1; Tsc2