Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing

Nat Commun. 2016 Oct 7;7:12972. doi: 10.1038/ncomms12972.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / biosynthesis
  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Enzyme Activation
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / genetics
  • Glycogen / metabolism
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / metabolism
  • Myosin Type II / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism*
  • Wound Healing / physiology*

Substances

  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • Insulin-Like Growth Factor I
  • Glycogen
  • Actomyosin
  • target of rapamycin protein, Drosophila
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 2
  • Myosin Type II