Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex

EMBO J. 2007 Jan 24;26(2):371-9. doi: 10.1038/sj.emboj.7601487. Epub 2006 Dec 21.

Abstract

In Drosophila and mammals, insulin signalling can increase growth, progression through G1/S, cell size and tissue size. Here, we analyse the way insulin affects cell size and cell-cycle progression in two haemocyte-derived Drosophila cell lines. Surprisingly, we find that although insulin increases cell size, it slows the rate at which these cells increase in number. By using BrdU pulse-chase to label S-phase cells and follow their progression through the cell cycle, we show that insulin delays progression through G2/M, thereby slowing cell division. The ability of insulin to slow progression through G2/M is independent of its ability to stimulate progression through G1/S, so is not a consequence of feedback by the cell-cycle machinery to maintain cell-cycle length. Insulin's effects on progression through G2/M are mediated by dTOR/dRaptor signalling. Partially inhibiting dTOR/dRaptor signalling by dsRNAi or mild rapamycin treatment can increase cell number in cultured haemocytes and the Drosophila wing, respectively. Thus, insulin signalling can influence cell number depending on a balance between its ability to accelerate progression through G1/S and delay progression through G2/M.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drosophila
  • Drosophila Proteins / metabolism*
  • G2 Phase / drug effects*
  • Insulin / pharmacology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Multiprotein Complexes / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinases
  • RNA Interference
  • S Phase / drug effects
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Wings, Animal / cytology
  • Wings, Animal / drug effects

Substances

  • Drosophila Proteins
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • raptor protein, Drosophila
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • target of rapamycin protein, Drosophila
  • TOR Serine-Threonine Kinases