| First Author | Nakagawa N | Year | 2013 |
| Journal | Glycobiology | Volume | 23 |
| Issue | 9 | Pages | 1066-74 |
| PubMed ID | 23723439 | Mgi Jnum | J:314382 |
| Mgi Id | MGI:6810695 | Doi | 10.1093/glycob/cwt043 |
| Citation | Nakagawa N, et al. (2013) HNK-1 sulfotransferase-dependent sulfation regulating laminin-binding glycans occurs in the post-phosphoryl moiety on alpha-dystroglycan. Glycobiology 23(9):1066-74 |
| abstractText | Dystroglycan (DG) is a cell surface glycoprotein that connects extracellular matrix molecules to the intracellular cytoskeleton, functioning as mechanical and signaling axes in various physiological events. Since the ligand-binding activity of DG strictly depends on O-mannosyl glycans attached to its extracellular alpha-DG subunit, aberrant glycosylation causes dystroglycanopathy, a subclass of congenital muscular dystrophy. Accumulating evidence shows that like-acetylglucosaminyltransferase (LARGE), a glycosyltransferase involved in the biosynthesis of a phosphodiester-linked modification on O-mannose, is essential for alpha-DG to gain the ligand-binding activity. We previously reported that human natural killer-1 sulfotransferase (HNK-1ST), which was originally reported as one of the enzymes responsible for HNK-1 glycoepitope, had an ability to suppress the glycosylation and the function of alpha-DG. In this study, we investigated how HNK-1ST regulates the glycosylation of alpha-DG using deletion and mutation analyses. We generated an alpha-DG mutant which has only one threonine residue capable of being modified by LARGE. Focusing on the single post-phosphoryl modification site, we found that HNK-1ST showed an almost complete inhibition of the LARGE-dependent modification and transferred a sulfate group to the phosphodiester-linked moiety on O-mannose. Furthermore, using an in vitro enzymatic assay system, we demonstrated that the sulfated alpha-DG by HNK-1ST is no longer glycosylated by LARGE. These results illustrate one possible glycosylation pathway where alpha-DG function is regulated by opposing actions of HNK-1ST and LARGE. |
