Tissue-specific coupling between insulin/IGF and TORC1 signaling via PRAS40 in Drosophila

Dev Cell. 2012 Jan 17;22(1):172-82. doi: 10.1016/j.devcel.2011.10.029.

Abstract

PRAS40 has recently been identified as a protein that couples insulin/IGF signaling (IIS) to TORC1 activation in cell culture; however, the physiological function of PRAS40 is not known. In this study, we investigate flies lacking PRAS40. Surprisingly, we find both biochemically and genetically that PRAS40 couples IIS to TORC1 activation in a tissue-specific manner, regulating TORC1 activity in ovaries but not in other tissues of the animal. PRAS40 thereby regulates fertility but not growth of the fly, allowing distinct physiological functions of TORC1 to be uncoupled. We also show that the main function of PRAS40 in vivo is to regulate TORC1 activity, and not to act as a downstream target and effector of TORC1. Finally, this work sheds some light on the question of whether TORC1 activity is coupled to IIS in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Cell Communication
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Female
  • Insulin / metabolism*
  • Organ Specificity
  • Ovary / cytology
  • Ovary / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Somatomedins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Drosophila Proteins
  • Insulin
  • PRAS40 protein, Drosophila
  • Phosphoproteins
  • RNA, Messenger
  • Somatomedins
  • TORC1 protein complex, Drosophila
  • Transcription Factors