{"doi":"10.1016/j.jbc.2025.110313","title":"Map of the neuronal O-glycoproteome reveals driver functions in the regulated secretory pathway","abstract":"Impairments in protein glycosylation, including O-GalNAc-type glycosylation, are linked to severe developmental disorders with prominent neurological involvement. However, the role of this glycosylation pathway at a cellular level is not yet fully understood. Here, we report a comprehensive map of GalNAc-type O-glycoproteins (>800) and O-glycosites (>4000) from neuronal tissues and cell lines and identify abundant O-glycosites within major classes of proteins involved in neuroplasticity, including axon guidance, membrane remodeling, and regulated vesicular secretion. Applying the map, we demonstrate that the regulated secretory pathway constitutes highly O-glycosylated proteins including Chromogranin A, a key player in dense core granulogenesis, and that correct O-glycosylation is important for its multimerization. Concurrently, genetically engineered neuronal cell lines deficient in O-glycosylation exhibit altered capacity for storing neurotransmitter noradrenaline and present enlarged neurotransmitter-containing dense core granules. Collectively, this map provides the foundation for uncovering critical roles for O-glycosylation in regulating neuroplasticity and provides evidence that dense core granule content is regulated by this pathway. Subjects: Granin, glycosylation, glycosaminoglycans, dense core granules (DCG), perineuronal net (PNN), mucin, central nervous system (CNS), neuron, neuroplasticity, neurotransmitter.","journal":"Journal of Biological Chemistry","year":2025,"id":541329,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.817,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1430066,"name":"Asli B. Topaktas","orcid":null,"position":1,"is_corresponding":false},{"id":630732,"name":"Leo Alexander Dworkin","orcid":"0000-0001-7185-6680","position":2,"is_corresponding":false},{"id":296368,"name":"John Hintze","orcid":"0000-0003-1420-7398","position":3,"is_corresponding":false},{"id":711179,"name":"Lasse H. Hansen","orcid":"0000-0001-6517-0412","position":4,"is_corresponding":false},{"id":1430067,"name":"Mahnaz Nikpour","orcid":null,"position":5,"is_corresponding":false},{"id":1307252,"name":"Jarkko J. Lackman","orcid":"0000-0002-0422-5157","position":6,"is_corresponding":false},{"id":378379,"name":"Christoffer K. Goth","orcid":"0000-0002-5766-1411","position":7,"is_corresponding":false},{"id":274816,"name":"Göran Larson","orcid":"0000-0002-2616-0366","position":8,"is_corresponding":false},{"id":1430068,"name":"Emily J. Shiplett","orcid":null,"position":9,"is_corresponding":false},{"id":296353,"name":"Andrew C. Edmondson","orcid":"0000-0003-0313-0743","position":10,"is_corresponding":false},{"id":400171,"name":"Zhaolan Zhou","orcid":"0000-0003-1401-0296","position":11,"is_corresponding":false},{"id":250208,"name":"Rebecca L. Miller","orcid":"0000-0002-1227-5891","position":12,"is_corresponding":false},{"id":630731,"name":"Hiren J. Joshi","orcid":"0000-0002-8192-2829","position":13,"is_corresponding":false},{"id":628479,"name":"Sergey Y. Vakhrushev","orcid":"0000-0002-0418-5765","position":14,"is_corresponding":false},{"id":296375,"name":"Katrine T. Schjoldager","orcid":"0000-0002-8592-6763","position":15,"is_corresponding":false},{"id":1055421,"name":"Thomas D. Madsen","orcid":"0000-0002-7598-4636","position":0,"is_corresponding":true}],"reference_count":128,"raw_metadata":null,"created_at":"2026-07-19T02:52:47.161928Z","pmid":"40449597","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":[]}