Abstract
Proteoglycans, a class of carbohydrate-modified proteins, often modulate growth factor signaling on the cell surface. However, the molecular mechanism by which proteoglycans regulate signal transduction is largely unknown. In this study, using a recently developed glycoproteomic method, we found that Windpipe (Wdp) is a novel chondroitin sulfate proteoglycan (CSPG) in Drosophila. Wdp is a single-pass transmembrane protein with leucin-rich repeat (LRR) motifs and bears three CS sugar chain attachment sites in the extracellular domain. Here we show that Wdp modulates the Hedgehog (Hh) pathway. In the wing disc, overexpression of wdp inhibits Hh signaling, which is dependent on its CS chains and the LRR motifs. The wdp null mutant flies show a specific defect (supernumerary scutellar bristles) known to be caused by Hh overexpression. RNA interference knockdown and mutant clone analyses showed that loss of wdp leads to the up-regulation of Hh signaling. Altogether, our study demonstrates a novel role of CSPGs in regulating Hh signaling.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 813-824 |
| Number of pages | 12 |
| Journal | Molecular biology of the cell |
| Volume | 31 |
| Issue number | 8 |
| DOIs | |
| State | Published - Mar 2020 |
Bibliographical note
Funding Information:We thank Melissa Harrison, Kate O’Connor-Giles, Jill Wildonger, Gary Struhl, Scott Selleck, Hugo Bellen, Gerald Rubin, Dianne Duncan, the Bloomington Drosophila Stock Center (National Institutes of Health [NIH] P40OD018537), the Transgenic RNAi Project at Harvard Medical School (NIH/National Institute of General Medical Sciences R01-GM08947), and the Drosophila Genomics Resource Center (NIH 2P40OD010949) for sharing fly strains and plasmids. We also thank the Proteomics Core Facility at the Sahlgrenska Academy, University of Gothenburg, Sweden, for running all the MS analyses. This work was supported by NIH (R35 GM131688) to H.N. and by the Swedish Research Council (8266) to G.L. M.T. held postdoctoral fellowships from the Japan Society for the Promotion of Science and the Uehara Memorial Foundation.
Funding Information:
We thank Melissa Harrison, Kate O?Connor-Giles, Jill Wildonger, Gary Struhl, Scott Selleck, Hugo Bellen, Gerald Rubin, Dianne Duncan, the Bloomington Drosophila Stock Center (National Institutes of Health [NIH] P40OD018537), the Transgenic RNAi Project at Harvard Medical School (NIH/National Institute of General Medical Sciences R01-GM08947), and the Drosophila Genomics Resource Center (NIH 2P40OD010949) for sharing fly strains and plasmids. We also thank the Proteomics Core Facility at the Sahlgrenska Academy, University of Gothenburg, Sweden, for running all the MS analyses. This work was supported by NIH (R35 GM131688) to H.N. and by the Swedish Research Council (8266) to G.L. M.T. held postdoctoral fellowships from the Japan Society for the Promotion of Science and the Uehara Memorial Foundation.
Publisher Copyright:
© 2020 Takemura et al.