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Wellstone Muscular Dystrophy Cooperative Research Center","award":["1U54NS053672"],"award-info":[{"award-number":["1U54NS053672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in multiple genes required for proper O-mannosylation of \u03b1-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-\u03b23-Xyl-\u03b13-)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 \u03b1-dystroglycan isolated from mouse heart and kidney is susceptible to exoglycosidase digestion of matriglycan, the functional, lower molecular weight \u03b1-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.<\/jats:p>","DOI":"10.1093\/glycob\/cwaa024","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T10:57:20Z","timestamp":1583751440000},"page":"817-829","source":"Crossref","is-referenced-by-count":21,"title":["HNK-1 sulfotransferase modulates \u03b1-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan"],"prefix":"10.1093","volume":"30","author":[{"given":"M Osman","family":"Sheikh","sequence":"first","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Venzke","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Department of Neurology, Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Department of Neurology, Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Yoshida-Moriguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Department of Neurology, Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N","family":"Glushka","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison V","family":"Nairn","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melina","family":"Galizzi","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelley W","family":"Moremen","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin P","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Department of Neurology, Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance","family":"Wells","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,3,9]]},"reference":[{"key":"2020111902062199200_ref1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.matbio.2005.05.006","article-title":"A simplified laminin nomenclature","volume":"24","author":"Aumailley","year":"2005","journal-title":"Matrix Biol"},{"key":"2020111902062199200_ref2","doi-asserted-by":"crossref","first-page":"29942","DOI":"10.1074\/jbc.272.47.29942","article-title":"Expression cloning of a cDNA encoding a sulfotransferase involved in the biosynthesis of the HNK-1 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