HNK-1 sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan
| Autor: | Kevin P. Campbell, David Venzke, John Glushka, M. Osman Sheikh, Mary E. Anderson, Lance Wells, Takako Yoshida-Moriguchi, Melina Galizzi, Kelley W. Moremen, Alison V. Nairn |
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| Rok vydání: | 2020 |
| Předmět: |
Glycan
Sulfotransferase Glycosylation animal structures Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound Sulfation Glucuronic Acid Exoglycosidase Glycosyltransferase Animals Dystroglycans 030304 developmental biology 0303 health sciences Genetic Disorders of Glycosylation biology Sulfatase 030302 biochemistry & molecular biology Carbohydrate sulfotransferase chemistry biology.protein Sulfotransferases |
| Zdroj: | Glycobiology |
| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/cwaa024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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