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Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E6993-E7002. doi: 10.1073/pnas.1610565113. Epub 2016 Oct 25.

Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs.

Author information

1
Cellular Organization and Signalling, National Centre for Biological Science, Tata Institute for Fundamental Research, Bangalore 560 065, India.
2
Cellular Organization and Signalling, National Centre for Biological Science, Tata Institute for Fundamental Research, Bangalore 560 065, India; mayor@ncbs.res.in.
3
Institute for Stem Cell Research and Regenerative Medicine, Bangalore 560 065, India.

Abstract

Endocytosis of ligand-receptor complexes regulates signal transduction during development. In particular, clathrin and dynamin-dependent endocytosis has been well studied in the context of patterning of the Drosophila wing disc, wherein apically secreted Wingless (Wg) encounters its receptor, DFrizzled2 (DFz2), resulting in a distinctive dorso-ventral pattern of signaling outputs. Here, we directly track the endocytosis of Wg and DFz2 in the wing disc and demonstrate that Wg is endocytosed from the apical surface devoid of DFz2 via a dynamin-independent CLIC/GEEC pathway, regulated by Arf1, Garz, and class I PI3K. Subsequently, Wg containing CLIC/GEEC endosomes fuse with DFz2-containing vesicles derived from the clathrin and dynamin-dependent endocytic pathway, which results in a low pH-dependent transfer of Wg to DFz2 within the merged and acidified endosome to initiate Wg signaling. The employment of two distinct endocytic pathways exemplifies a mechanism wherein cells in tissues leverage multiple endocytic pathways to spatially regulate signaling.

KEYWORDS:

Garz localization; Wingless signaling; clathrin and dynamin-independent endocytosis; pH of endosome; wing disc development

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