Journal article
HNK-1 sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan
Glycobiology (Oxford), Vol.30(10), pp.817-829
10/01/2020
DOI: 10.1093/glycob/cwaa024
PMCID: PMC7673472
PMID: 32149355
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.
Details
- Title: Subtitle
- HNK-1 sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan
- Creators
- M Osman Sheikh - Complex Carbohydrate Research CenterDavid Venzke - Department of Molecular Physiology and BiophysicsMary E Anderson - Department of Molecular Physiology and BiophysicsTakako Yoshida-Moriguchi - Department of Molecular Physiology and BiophysicsJohn N Glushka - Complex Carbohydrate Research CenterAlison V Nairn - Complex Carbohydrate Research CenterMelina Galizzi - Complex Carbohydrate Research CenterKelley W Moremen - Complex Carbohydrate Research CenterKevin P Campbell - Department of Molecular Physiology and BiophysicsLance Wells - Complex Carbohydrate Research Center
- Resource Type
- Journal article
- Publication Details
- Glycobiology (Oxford), Vol.30(10), pp.817-829
- Publisher
- Oxford University Press
- DOI
- 10.1093/glycob/cwaa024
- PMID
- 32149355
- PMCID
- PMC7673472
- ISSN
- 0959-6658
- eISSN
- 1460-2423
- Grant note
- R01GM111939; P41GM103390; P01GM107012; R01GM130915 / ; ; 1U54NS053672 / ; ;
- Language
- English
- Date published
- 10/01/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068280202771
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