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Wingless secretion promotes and requires retromer-dependent cycling of Wntless

Nature Cell Biology volume 10, pages 178–185 (2008)Cite this article

Abstract

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 Wnts1,2,3. 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 yeast4. 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.

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Figure 1: The presence of Drosophila Wnt proteins alters Wls levels.
Figure 2: Endogenous Wls accumulates in the Golgi in Wg-producing cells.
Figure 3: Reduction of retromer function inhibits Wg secretion.
Figure 4: Reduction of retromer function results in a loss of Wls in Wg-producing cells.
Figure 5: Wls is localized at the cell membrane and rescues loss-of-retromer function.

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Acknowledgements

We thank: S. Eaton, M. A. Lilly, G. Morata and G. Struhl for providing fly stocks and antibodies; B. Dickson and the VDRC team for providing RNAi lines; R. Korswagen for sharing unpublished observations; V. Katanaev and S. Luschnig for critical reading of the manuscript; and members of our lab for discussions. This work was supported by the Swiss National Science Foundation and the Kanton of Zürich.

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  1. Fillip Port, Marco Kuster and Patrick Herr: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut für Molekularbiologie, Universität Zürich, Winterthurerstr. 190, Zürich, CH-8057, Switzerland

    Fillip Port, Marco Kuster, Patrick Herr, Edy Furger, Carla Bänziger, George Hausmann & Konrad Basler

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  1. Fillip Port
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Correspondence to Konrad Basler.

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Supplementary Figures S1, S2, s3, S4 and S5, Supplementary Note and Supplementary Methods (PDF 1452 kb)

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Port, F., Kuster, M., Herr, P. et al. Wingless secretion promotes and requires retromer-dependent cycling of Wntless. Nat Cell Biol 10, 178–185 (2008). https://doi.org/10.1038/ncb1687

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