title: TORC2 mediates the heat stress response in Drosophila by promoting the formation of stress granules.
abstract: The kinase TOR is found in two complexes, TORC1, which is involved in growth control, and TORC2, whose roles are less well defined. Here, we asked whether TORC2 has a role in sustaining cellular stress. We show that TORC2 inhibition in Drosophila melanogaster leads to a reduced tolerance to heat stress, whereas sensitivity to other stresses is not affected. Accordingly, we show that upon heat stress, both in the animal and Drosophila cultured S2 cells, TORC2 is activated and is required for maintaining the level of its known target, Akt1 (also known as PKB). We show that the phosphorylation of the stress-activated protein kinases is not modulated by TORC2 nor is the heat-induced upregulation of heat-shock proteins. Instead, we show, both in vivo and in cultured cells, that TORC2 is required for the assembly of heat-induced cytoprotective ribonucleoprotein particles, the pro-survival stress granules. These granules are formed in response to protein translation inhibition imposed by heat stress that appears to be less efficient in the absence of TORC2 function. We propose that TORC2 mediates heat resistance in Drosophila by promoting the cell autonomous formation of stress granules.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Irena
authors.initials: I
authors.lastname: Jevtov
authors.affiliation: Hubrecht Institute of the KNAW and UMC Utrecht, Uppsalalaan 8, Utrecht 3584 CT, Netherlands.
authors.forename: Margarita
authors.initials: M
authors.lastname: Zacharogianni
authors.affiliation: Hubrecht Institute of the KNAW and UMC Utrecht, Uppsalalaan 8, Utrecht 3584 CT, Netherlands.
authors.forename: Marinke M
authors.initials: MM
authors.lastname: van Oorschot
authors.affiliation: Cellular Protein Chemistry, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors.forename: Guus
authors.initials: G
authors.lastname: van Zadelhoff
authors.affiliation: Hubrecht Institute of the KNAW and UMC Utrecht, Uppsalalaan 8, Utrecht 3584 CT, Netherlands.
authors.forename: Angelica
authors.initials: A
authors.lastname: Aguilera-Gomez
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Vuillez
authors.affiliation: Cellular Protein Chemistry, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors.forename: Ineke
authors.initials: I
authors.lastname: Braakman
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland stocker@imsb.biol.ethz.ch c.rabouille@umcutrecht.nl.
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.affiliation: Hubrecht Institute of the KNAW and UMC Utrecht, Uppsalalaan 8, Utrecht 3584 CT, Netherlands Department of Cell Biology, UMC Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands stocker@imsb.biol.ethz.ch c.rabouille@umcutrecht.nl.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rabouille
mesh_terms: D000818:Animals; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D018869:Heat-Shock Response / Q000502:physiology*; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D046912:Multiprotein Complexes; C494917:Akt1 protein, Drosophila; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Drosophila S2 cells; Heat stress; Heat-shock protein; PKB; Rictor; SAPK; Sin1; Stress granules; TORC2; Translation