title: Godzilla-dependent transcytosis promotes Wingless signalling in Drosophila wing imaginal discs.
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.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 9A, 40539 Gothenburg, Sweden.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Palmer
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Alexandre
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kakugawa
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Beckett
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gaugue
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 9A, 40539 Gothenburg, Sweden.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Palmer
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vincent
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D060227:Imaginal Discs / Q000196:embryology / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D018613:Microscopy, Confocal; D034622:RNA Interference; D015398:Signal Transduction; D057900:Transcytosis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000196:embryology / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D049452:Green Fluorescent Proteins; D044767:Ubiquitin-Protein Ligases; C000609849:gzl protein, Drosophila