Wingless secretion promotes and requires retromer-dependent cycling of Wntless.
Wnt ligands are lipid-modified, secreted glycoproteins that control multiple steps during embryogenesis and adult-tissue homeostasis. Little is known about the mechanisms underlying Wnt secretion. Recently, Wntless (Wls/Evi/Srt) was identified as a conserved multi-pass transmembrane protein whose function seems to be dedicated to promoting the release of Wnts. Here, we describe Wls accumulation in the Golgi apparatus of Wnt/Wingless (Wg)-producing cells in Drosophila, and show that this localization is essential for Wg secretion. Moreover, Wls localization and levels critically depend on retromer, a conserved protein complex that mediates endosome-to-Golgi protein trafficking in yeast. In the absence of the retromer components Dvps35 or Dvps26, but in presence of Wg, Wls is degraded and Wg secretion impaired. Our results indicate that Wg, clathrin-mediated endocytosis and retromer sustain a Wls traffic loop from the Golgi to the plasma membrane and back to the Golgi, thereby enabling Wls to direct Wnt secretion.
Port
Fillip
F
Institut für Molekularbiologie, Universität Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
Kuster
Marco
M
Herr
Patrick
P
Furger
Edy
E
Bänziger
Carla
C
Hausmann
George
G
Basler
Konrad
K
D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D033921:Vesicular Transport Proteins; C528433:Vps26 protein, Drosophila; C527271:Vps35 protein, Drosophila; C511046:Wls protein, Drosophila; D051153:Wnt Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila