CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc

  1. Romero-Pozuelo, Jesús 1
  2. Demetriades, Constantinos
  3. Schroeder, Phillip
  4. Teleman, Aurelio A.
  1. 1 German Cancer Research Center
    info

    German Cancer Research Center

    Heidelberg, Alemania

    ROR https://ror.org/04cdgtt98

Revista:
Developmental Cell

ISSN: 1534-5807

Año de publicación: 2017

Volumen: 42

Número: 4

Páginas: 376-387.e5

Tipo: Artículo

DOI: 10.1016/J.DEVCEL.2017.07.019 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Developmental Cell

Resumen

The molecular mechanisms regulating animal tissue size during development are unclear. This question has been extensively studied in the Drosophila wing disc. Although cell growth is regulated by the kinase TORC1, no readout exists to visualize TORC1 activity in situ in Drosophila. Both the cell cycle and the morphogen Dpp are linked to tissue growth, but whether they regulate TORC1 activity is not known. We develop here an anti-phospho-dRpS6 antibody that detects TORC1 activity in situ. We find, unexpectedly, that TORC1 activity in the wing disc is patchy. This is caused by elevated TORC1 activity at the cell cycle G1/S transition due to CycD/Cdk4 phosphorylating TSC1/2. We find that TORC1 is also activated independently of CycD/Cdk4 when cells with different levels of Dpp signaling or Brinker protein are juxtaposed. We thereby characterize the spatial distribution of TORC1 activity in a developing organ.

Información de financiación

Financiadores

  • Deutsche Forschungsgemeinschaft Sonderforschungsbereich
    • SFB1036
  • University of Heidelberg Cell Networks
    • EcTop6

Referencias bibliográficas

  • Affolter, (2007), Nat. Rev. Genet., 8, pp. 663, 10.1038/nrg2166
  • Akiyama, (2015), Nature, 527, pp. 375, 10.1038/nature15730
  • Astrinidis, (2003), J. Biol. Chem., 278, pp. 51372, 10.1074/jbc.M303956200
  • Bar-Peled, (2014), Trends Cell Biol., 24, pp. 400, 10.1016/j.tcb.2014.03.003
  • Ben-Sahra, (2013), Science, 339, pp. 1323, 10.1126/science.1228792
  • Ben-Sahra, (2016), Science, 351, pp. 728, 10.1126/science.aad0489
  • Betz, (2013), J. Cell Biol., 203, pp. 563, 10.1083/jcb.201306041
  • Boyer, (2008), Mol. Cell Biochem., 307, pp. 59, 10.1007/s11010-007-9584-5
  • Burke, (1996), Development, 122, pp. 2261, 10.1242/dev.122.7.2261
  • Campbell, (1999), Cell, 96, pp. 553, 10.1016/S0092-8674(00)80659-5
  • Carroll, (2016), Elife, 5, pp. e11058, 10.7554/eLife.11058
  • Datar, (2000), EMBO J., 19, pp. 4543, 10.1093/emboj/19.17.4543
  • Demetriades, (2014), Cell, 156, pp. 786, 10.1016/j.cell.2014.01.024
  • Demetriades, (2016), Nat. Commun., 7, pp. 10662, 10.1038/ncomms10662
  • Doumpas, (2013), EMBO Rep., 14, pp. 261, 10.1038/embor.2013.1
  • Edelmann, (1996), J. Biol. Chem., 271, pp. 963, 10.1074/jbc.271.2.963
  • Emmerich, (2004), Genetics, 168, pp. 867, 10.1534/genetics.104.027417
  • Fingar, (2004), Mol. Cell Biol., 24, pp. 200, 10.1128/MCB.24.1.200-216.2004
  • Francis, (2010), Curr. Biol., 20, pp. 1799, 10.1016/j.cub.2010.08.055
  • Gelbart, (1989), Development, 107, pp. 65, 10.1242/dev.107.Supplement.65
  • Gilboa, (2004), Curr. Biol., 14, pp. 981, 10.1016/j.cub.2004.05.049
  • Gross, (2012), Nat. Cell Biol., 14, pp. 1036, 10.1038/ncb2574
  • Harmansa, (2015), Nature, 527, pp. 317, 10.1038/nature15712
  • Huang, (2008), Biochem. J., 412, pp. 179, 10.1042/BJ20080281
  • Jazwinska, (1999), Cell, 96, pp. 563, 10.1016/S0092-8674(00)80660-1
  • Jewell, (2013), Trends Biochem. Sci., 38, pp. 233, 10.1016/j.tibs.2013.01.004
  • Johnston, (2002), Bioessays, 24, pp. 54, 10.1002/bies.10021
  • Kim, (2008), Nat. Cell Biol., 10, pp. 935, 10.1038/ncb1753
  • Kim, (2017), Dev. Cell, 42, pp. 363, 10.1016/j.devcel.2017.07.020
  • Kitagawa, (1996), EMBO J., 15, pp. 7060, 10.1002/j.1460-2075.1996.tb01097.x
  • Lane, (1993), Nature, 363, pp. 170, 10.1038/363170a0
  • Laplante, (2012), Cell, 149, pp. 274, 10.1016/j.cell.2012.03.017
  • Leevers, (1996), EMBO J., 15, pp. 6584, 10.1002/j.1460-2075.1996.tb01049.x
  • Loewith, (2011), Genetics, 189, pp. 1177, 10.1534/genetics.111.133363
  • Magnuson, (2012), Biochem. J., 441, pp. 1, 10.1042/BJ20110892
  • Martin-Castellanos, (2002), Development, 129, pp. 1003, 10.1242/dev.129.4.1003
  • Meyer, (2000), EMBO J., 19, pp. 4533, 10.1093/emboj/19.17.4533
  • Minami, (1999), Nature, 398, pp. 242, 10.1038/18451
  • Muller, (2003), Cell, 113, pp. 221, 10.1016/S0092-8674(03)00241-1
  • Nellen, (1996), Cell, 85, pp. 357, 10.1016/S0092-8674(00)81114-9
  • Neufeld, (1998), Cell, 93, pp. 1183, 10.1016/S0092-8674(00)81462-2
  • Pallares-Cartes, (2012), Dev. Cell, 22, pp. 172, 10.1016/j.devcel.2011.10.029
  • Robitaille, (2013), Science, 339, pp. 1320, 10.1126/science.1228771
  • Rogulja, (2005), Cell, 123, pp. 449, 10.1016/j.cell.2005.08.030
  • Rosner, (2011), Cell Cycle, 10, pp. 3608, 10.4161/cc.10.20.17855
  • Satyanarayana, (2009), Oncogene, 28, pp. 2925, 10.1038/onc.2009.170
  • Schindelin, (2012), Nat. Methods, 9, pp. 676, 10.1038/nmeth.2019
  • Schwank, (2010), Cold Spring Harb. Perspect. Biol., 2, pp. a001669, 10.1101/cshperspect.a001669
  • Schwank, (2008), Development, 135, pp. 4003, 10.1242/dev.025635
  • Schwank, (2012), Science, 335, pp. 401, 10.1126/science.1210997
  • Shingleton, (2010), Organogenesis, 6, pp. 76, 10.4161/org.6.2.10375
  • Sullivan, (2000)
  • Tapon, (2001), Cell, 105, pp. 345, 10.1016/S0092-8674(01)00332-4
  • Teleman, (2000), Cell, 103, pp. 971, 10.1016/S0092-8674(00)00199-9
  • Thacker, (2003), Curr. Biol., 13, pp. 53, 10.1016/S0960-9822(02)01400-8
  • Tiebe, (2015), Dev. Cell, 33, pp. 272, 10.1016/j.devcel.2015.03.013
  • Tsokanos, (2016), EMBO J., 35, pp. 1058, 10.15252/embj.201593118
  • Wakiyama, (2005), Biochem. Biophys. Res. Commun., 331, pp. 1163, 10.1016/j.bbrc.2005.03.240
  • Wartlick, (2011), Science, 331, pp. 1154, 10.1126/science.1200037
  • Wiersdorff, (1996), Development, 122, pp. 2153, 10.1242/dev.122.7.2153
  • Zacharek, (2005), Cancer Res., 65, pp. 11354, 10.1158/0008-5472.CAN-05-2236
  • Zhang, (2000), Genes Dev., 14, pp. 2712, 10.1101/gad.835000
  • Zielke, (2014), Cell Rep., 7, pp. 588, 10.1016/j.celrep.2014.03.020