期刊
MOLECULAR BIOLOGY OF THE CELL
卷 31, 期 8, 页码 813-824出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E19-06-0327
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资金
- Bloomington Drosophila Stock Center (National Institutes of Health [NIH]) [P40OD018537]
- Transgenic RNAi Project at Harvard Medical School (NIH/National Institute of General Medical Sciences) [R01GM08947]
- Drosophila Genomics Resource Center [NIH 2P40OD010949]
- NIH [R35 GM131688]
- Swedish Research Council [8266]
- Japan Society for the Promotion of Science
- Uehara Memorial Foundation
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.
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