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- Title
HNK-1 sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan.
- Authors
Sheikh, M Osman; Venzke, David; Anderson, Mary E; Yoshida-Moriguchi, Takako; Glushka, John N; Nairn, Alison V; Galizzi, Melina; Moremen, Kelley W; Campbell, Kevin P; Wells, Lance
- Abstract
Mutations in multiple genes required for proper O-mannosylation of α-dystroglycan are causal for congenital/limb-girdle muscular dystrophies and abnormal brain development in mammals. Previously, we and others further elucidated the functional O -mannose glycan structure that is terminated by matriglycan, [(-GlcA-β3-Xyl-α3-) n ]. This repeating disaccharide serves as a receptor for proteins in the extracellular matrix. Here, we demonstrate in vitro that HNK-1 sulfotransferase (HNK-1ST/carbohydrate sulfotransferase) sulfates terminal glucuronyl residues of matriglycan at the 3-hydroxyl and prevents further matriglycan polymerization by the LARGE1 glycosyltransferase. While α-dystroglycan isolated from mouse heart and kidney is susceptible to exoglycosidase digestion of matriglycan, the functional, lower molecular weight α-dystroglycan detected in brain, where HNK-1ST expression is elevated, is resistant. Removal of the sulfate cap by a sulfatase facilitated dual-glycosidase digestion. Our data strongly support a tissue specific mechanism in which HNK-1ST regulates polymer length by competing with LARGE for the 3-position on the nonreducing GlcA of matriglycan.
- Subjects
GLUCURONIC acid; EXTRACELLULAR matrix proteins; GLYCOSYLATION; MUSCULAR dystrophy; GLYCAN structure
- Publication
Glycobiology, 2020, Vol 30, Issue 10, p817
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cwaa024