Drosophila Melted modulates FOXO and TOR activity

Dev Cell. 2005 Aug;9(2):271-81. doi: 10.1016/j.devcel.2005.07.004.

Abstract

The insulin/PI3K signaling pathway controls both tissue growth and metabolism. Here, we identify Melted as a new modulator of this pathway in Drosophila. Melted interacts with both Tsc1 and FOXO and can recruit these proteins to the cell membrane. We provide evidence that in the melted mutant, TOR activity is reduced and FOXO is activated. The melted mutant condition mimics the effects of nutrient deprivation in a normal animal, producing an animal with 40% less fat than normal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / physiology
  • Animals
  • Cell Membrane / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / physiology*
  • Enzyme Activation
  • Forkhead Transcription Factors
  • Humans
  • Insulin / physiology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Binding
  • Protein Kinases
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • TSC1 protein, human
  • Transcription Factors
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins
  • melt protein, Drosophila
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • target of rapamycin protein, Drosophila
  • TOR Serine-Threonine Kinases