Abstract
AbstractProteoglycans (PGs) are composed of a core protein and one or more chains of glycosaminoglycans (GAGs). The highly heterogeneous GAG chains play an irreplaceable role in the functions of PGs. However, the lack of an approach to control the exact structure of GAG chains conjugated to PGs tremendously hinders functional studies of PGs. Herein, by using glypican-3 as a model, we establish an aldehyde tag-based approach to assemble PGs with specific GAG chains on the surface of living cells. We show that the engineered glypican-3 can regulate Wnt and Hedgehog signaling like the wild type. Furthermore, we also present a method for studying the interaction of PGs with their target glycoproteins by combining the assembly of PGs carrying specific GAG chains with metabolic glycan labeling, and most importantly, we obtain evidence of GPC3 directly interacting with Frizzled. In conclusion, this study provides a very useful platform for structural and functional studies of PGs with specific GAG chains.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference50 articles.
1. Afratis, N. A. et al. Syndecans - key regulators of cell signaling and biological functions. FEBS J. 284, 27–41 (2017).
2. Chakraborty, S. et al. An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nat. Commun. 6, 6184 (2015).
3. Filmus, J. & Capurro, M. The role of glypicans in Hedgehog signaling. Matrix biology: journal of the International Society for. Matrix Biol. 35, 248–252 (2014).
4. Kronenberg, H. M. Developmental regulation of the growth plate. Nature 423, 332–336 (2003).
5. Koziel, L., Kunath, M., Kelly, O. G. & Vortkamp, A. Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev. Cell 6, 801–813 (2004).
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献