1. Ykt6-dependent endosomal recycling is required for Wnt secretion in the Drosophila wing epithelium
- Author
-
Karen Linnemannstöns, Lena Nitsch, Adi Danieli, Ferdinand Grawe, Andreas Wodarz, Pradhipa Karuna, Julia Christina Gross, Denise Müller, Mona Honemann-Capito, Jeanette Clarissa Kittel, and Leonie Witte
- Subjects
Cell signaling ,animal structures ,Endosome ,Endosomes ,Biology ,Endocytosis ,Epithelium ,12. Responsible consumption ,Endosomal sorting ,R-SNARE Proteins ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Drosophila Proteins ,Wings, Animal ,Compartment (development) ,Secretion ,Molecular Biology ,Wnt signalling ,030304 developmental biology ,0303 health sciences ,Wnt signaling pathway ,Morphogen trafficking ,Cell biology ,Wnt Proteins ,Imaginal disc ,Drosophila melanogaster ,Wnt secretion ,030217 neurology & neurosurgery ,Research Article ,Developmental Biology ,Morphogen - Abstract
Morphogens are important signalling molecules for tissue development and their secretion requires tight regulation. In the wing imaginal disc of flies, the morphogen Wnt/Wingless is apically presented by the secreting cell and re-internalized before final long-range secretion. Why Wnt molecules undergo these trafficking steps and the nature of the regulatory control within the endosomal compartment remain unclear. Here, we have investigated how Wnts are sorted at the level of endosomes by the versatile v-SNARE Ykt6. Using in vivo genetics, proximity-dependent proteomics and in vitro biochemical analyses, we show that most Ykt6 is present in the cytosol, but can be recruited to de-acidified compartments and recycle Wnts to the plasma membrane via Rab4-positive recycling endosomes. Thus, we propose a molecular mechanism by which producing cells integrate and leverage endocytosis and recycling via Ykt6 to coordinate extracellular Wnt levels., Summary: SNARE-dependent secondary secretion via Rab4 recycling endosomes plays an important role in coordinating long-range extracellular levels of the hydrophobic morphogen Wnt/Wingless.
- Published
- 2020