Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex.
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.
Wu
Mary Y W
MY
Growth Regulation Laboratory, Cancer Research UK London Research Institute, London, UK.
Cully
Megan
M
Andersen
Ditte
D
Leevers
Sally J
SJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D016195:G2 Phase / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D046912:Multiprotein Complexes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases; D034622:RNA Interference; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014921:Wings, Animal / Q000166:cytology / Q000187:drug effects
D029721:Drosophila Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; C518293:raptor protein, Drosophila; C416303:target of rapamycin protein, Drosophila