Lipoprotein particles are required for Hedgehog and Wingless signalling

Nature. 2005 May 5;435(7038):58-65. doi: 10.1038/nature03504.

Abstract

Wnt and Hedgehog family proteins are secreted signalling molecules (morphogens) that act at both long and short range to control growth and patterning during development. Both proteins are covalently modified by lipid, and the mechanism by which such hydrophobic molecules might spread over long distances is unknown. Here we show that Wingless, Hedgehog and glycophosphatidylinositol-linked proteins copurify with lipoprotein particles, and co-localize with them in the developing wing epithelium of Drosophila. In larvae with reduced lipoprotein levels, Hedgehog accumulates near its site of production, and fails to signal over its normal range. Similarly, the range of Wingless signalling is narrowed. We propose a novel function for lipoprotein particles, in which they act as vehicles for the movement of lipid-linked morphogens and glycophosphatidylinositol-linked proteins.

MeSH terms

  • Animals
  • Biological Transport
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Epithelium / embryology
  • Epithelium / metabolism
  • Glycosylphosphatidylinositols / metabolism
  • Hedgehog Proteins
  • Hydrophobic and Hydrophilic Interactions
  • Larva / metabolism
  • Lipid Metabolism
  • Lipids / deficiency
  • Lipoproteins / genetics
  • Lipoproteins / isolation & purification
  • Lipoproteins / metabolism*
  • Protein Transport
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • Signal Transduction*
  • Solubility
  • Wings, Animal / embryology
  • Wings, Animal / metabolism
  • Wnt1 Protein

Substances

  • Drosophila Proteins
  • Glycosylphosphatidylinositols
  • Hedgehog Proteins
  • Lipids
  • Lipoproteins
  • Proto-Oncogene Proteins
  • Wnt1 Protein
  • lipophorin
  • wg protein, Drosophila
  • hh protein, Drosophila