Drosophila ALS Regulates Growth and Metabolism Through Functional Interaction With Insulin-Like Peptides

Cell Metab. 2008 Apr;7(4):333-8. doi: 10.1016/j.cmet.2008.02.003.

Abstract

In metazoans, factors of the insulin family control growth, metabolism, longevity, and fertility in response to environmental cues. In Drosophila, a family of seven insulin-like peptides, called Dilps, activate a common insulin receptor. Some Dilp peptides carry both metabolic and growth functions, raising the possibility that various binding partners specify their functions. Here we identify dALS, the fly ortholog of the vertebrate insulin-like growth factor (IGF)-binding protein acid-labile subunit (ALS), as a Dilp partner that forms a circulating trimeric complex with one molecule of Dilp and one molecule of Imp-L2, an IgG-family molecule distantly related to mammalian IGF-binding proteins (IGFBPs). We further show that dALS antagonizes Dilp function to control animal growth as well as carbohydrate and fat metabolism. These results lead us to propose an evolutionary perspective in which ALS function appeared prior to the separation between metabolic and growth effects that are associated with vertebrate insulin and IGFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Nutritional Physiological Phenomena
  • Animals
  • Blotting, Western
  • Drosophila / growth & development*
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Energy Metabolism
  • Gene Expression Regulation
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • Larva / growth & development
  • Larva / metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Somatomedins / metabolism*
  • Stress, Physiological

Substances

  • Drosophila Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Multiprotein Complexes
  • Somatomedins
  • acid-labile subunit, Drosophila