Godzilla-dependent transcytosis promotes Wingless signalling in Drosophila wing imaginal discs

Nat Cell Biol. 2016 Apr;18(4):451-7. doi: 10.1038/ncb3325. Epub 2016 Mar 14.

Abstract

The apical and basolateral membranes of epithelia are insulated from each other, preventing the transfer of extracellular proteins from one side to the other. Thus, a signalling protein produced apically is not expected to reach basolateral receptors. Evidence suggests that Wingless, the main Drosophila Wnt, is secreted apically in the embryonic epidermis. However, in the wing imaginal disc epithelium, Wingless is mostly seen on the basolateral membrane where it spreads from secreting to receiving cells. Here we examine the apico-basal movement of Wingless in Wingless-producing cells of wing imaginal discs. We find that it is presented first on the apical surface before making its way to the basolateral surface, where it is released and allowed to interact with signalling receptors. We show that Wingless transcytosis involves dynamin-dependent endocytosis from the apical surface. Subsequent trafficking from early apical endosomes to the basolateral surface requires Godzilla, a member of the RNF family of membrane-anchored E3 ubiquitin ligases. Without such transport, Wingless signalling is strongly reduced in this tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Endosomes / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Imaginal Discs / embryology
  • Imaginal Discs / metabolism*
  • In Situ Hybridization, Fluorescence
  • Microscopy, Confocal
  • RNA Interference
  • Signal Transduction*
  • Transcytosis
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Wings, Animal / embryology
  • Wings, Animal / metabolism*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*

Substances

  • Drosophila Proteins
  • Wnt1 Protein
  • wg protein, Drosophila
  • Green Fluorescent Proteins
  • Ubiquitin-Protein Ligases
  • gzl protein, Drosophila