{"doi":"10.1016/j.jbc.2023.105361","title":"Multiple N-linked glycosylation sites critically modulate the synaptic abundance of neuroligin isoforms","abstract":"In recent years, elegant glycomic and glycoproteomic approaches have revealed an intricate glycosylation profile of mammalian brain with enormous spatial and temporal diversities. Nevertheless, at a cellular level, it is unclear how these post-translational modifications affect various proteins to influence crucial neuronal properties. Here, we have investigated the impact of N-linked glycosylation on neuroligins (NLGNs), a class of cell-adhesion molecules that play instructive roles in synapse organization. We found that endogenous NLGN proteins are differentially glycosylated across several regions of murine brain in a sex-independent but isoform-dependent manner. In both rodent primary neurons derived from brain sections and human neurons differentiated from stem cells, all NLGN variants were highly enriched with multiple N-glycan subtypes, which cumulatively ensured their efficient trafficking to the cell surface. Removal of these N-glycosylation residues only had a moderate effect on NLGNs' stability or expression levels but particularly enhanced their retention at the endoplasmic reticulum. As a result, the glycosylation-deficient NLGNs exhibited considerable impairments in their dendritic distribution and postsynaptic accumulation, which in turn, virtually eliminated their ability to recruit presynaptic terminals and significantly reduced NLGN overexpression-induced assemblies of both glutamatergic and GABAergic synapse structures. Therefore, our results highlight an essential mechanistic contribution of N-linked glycosylations in facilitating the appropriate secretory transport of a major synaptic cell-adhesion molecule and promoting its cellular function in neurons.","journal":"Journal of Biological Chemistry","year":2023,"id":355250,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":878129,"name":"Thomas P. Cast","orcid":null,"position":1,"is_corresponding":false},{"id":694566,"name":"Laurie S. Minamide","orcid":null,"position":2,"is_corresponding":false},{"id":996458,"name":"Zephyr Lenninger","orcid":"0000-0003-1192-9037","position":3,"is_corresponding":false},{"id":417433,"name":"James R. Bamburg","orcid":"0000-0003-3767-3586","position":4,"is_corresponding":false},{"id":351569,"name":"Soham Chanda","orcid":"0000-0002-2327-6224","position":5,"is_corresponding":false},{"id":877667,"name":"Orion Benner","orcid":"0009-0007-4940-7265","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:16.394812Z","pmid":"37865312","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":[]}