{"doi":"10.1093/glycob/cwaa024","title":"HNK-1 sulfotransferase modulates α-dystroglycan glycosylation by 3-O-sulfation of glucuronic acid on matriglycan","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.","journal":"Glycobiology","year":2020,"id":68988,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365960,"name":"David Venzke","orcid":"0000-0001-8180-9562","position":1,"is_corresponding":false},{"id":365961,"name":"Mary E. Anderson","orcid":"0000-0001-5342-530X","position":2,"is_corresponding":false},{"id":367727,"name":"Takako Yoshida‐Moriguchi","orcid":null,"position":3,"is_corresponding":false},{"id":365962,"name":"John Glushka","orcid":"0000-0002-6615-0496","position":4,"is_corresponding":false},{"id":365963,"name":"Alison V. Nairn","orcid":"0000-0002-4453-7593","position":5,"is_corresponding":false},{"id":367728,"name":"Melina Galizzi","orcid":null,"position":6,"is_corresponding":false},{"id":53135,"name":"Kelley W. Moremen","orcid":"0000-0003-1768-582X","position":7,"is_corresponding":false},{"id":365964,"name":"Kevin P. Campbell","orcid":"0000-0003-2066-5889","position":8,"is_corresponding":false},{"id":227815,"name":"Lance Wells","orcid":"0000-0003-4956-5363","position":9,"is_corresponding":false},{"id":365959,"name":"M. Osman Sheikh","orcid":"0000-0002-9481-8318","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:42:22.705573Z","pmid":"32149355","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}