title: Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing.
abstract: The TOR and Insulin/IGF signalling (IIS) network controls growth, metabolism and ageing. Although reducing TOR or insulin signalling can be beneficial for ageing, it can be detrimental for wound healing, but the reasons for this difference are unknown. Here we show that IIS is activated in the cells surrounding an epidermal wound in Drosophila melanogaster larvae, resulting in PI3K activation and redistribution of the transcription factor FOXO. Insulin and TOR signalling are independently necessary for normal wound healing, with FOXO and S6K as their respective effectors. IIS is specifically required in cells surrounding the wound, and the effect is independent of glycogen metabolism. Insulin signalling is needed for the efficient assembly of an actomyosin cable around the wound, and constitutively active myosin II regulatory light chain suppresses the effects of reduced IIS. These findings may have implications for the role of insulin signalling and FOXO activation in diabetic wound healing.
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicherstr. 47a, Cologne 50674, Germany.|Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne 50931, Germany.|Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.
authors.forename: Parisa
authors.initials: P
authors.lastname: Kakanj
authors.affiliation: Institute of Biology Valrose (IBV), University of Nice-Sophia Antipolis, Nice Cedex 2 06108, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moussian
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne 50931, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne 50931, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Bustos
authors.affiliation: Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.|Department of Dermatology, University of Cologne, Kerpenerstr. 62, Cologne 50937, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.
authors.forename: Sabine A
authors.initials: SA
authors.lastname: Eming
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne 50931, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.|Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicherstr. 47a, Cologne 50674, Germany.|Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.|European Molecular Biology Laboratory, Meyerhofstr. 1, Heidelberg 69117, Germany.
authors.forename: Maria
authors.identifier: http://orcid.org/0000-0001-7097-348X
authors.initials: M
authors.lastname: Leptin
mesh_terms: D000205:Actomyosin / Q000096:biosynthesis; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004789:Enzyme Activation; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000205:Actomyosin; D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D006003:Glycogen; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D024462:Myosin Type II; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C477334:FOXO protein, Drosophila; C416303:target of rapamycin protein, Drosophila; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2