{"doi":"10.1101/2020.01.18.911487","title":"Splicing of the SynGAP Carboxyl-Terminus Enables Isoform-Specific Tuning of NMDA Receptor Signaling Linked to Cognitive Function","abstract":"Summary SynGAP-α1 is a splice variant of the neurodevelopmental disorder risk gene, SYNGAP1/Syngap1 . α1 encodes the C-terminal PDZ binding motif (PBM) that promotes liquid-liquid phase separation, a candidate process for postsynaptic density organization within excitatory synapses. However, it remains unknown how the endogenous SynGAP PBM regulates synapse properties and related cognitive functions. We found that a major PBM function in mice is to limit the mobility of SynGAP-α1 in response to NMDA receptor activation. Genetic disruption of the PBM increased SynGAP-α1 mobility to levels consistent with other non-PBM-containing C-terminal isoforms. This resulted in a lowering of the threshold for NMDA receptor-dependent signaling required for plasticity, leading to aberrant strengthening of excitatory synapses in spontaneously active neurons. PBM-deficient animals also exhibited a lower seizure threshold, disrupted LTP, and impaired cognition. Thus, the PBM enables isoform-specific SynGAP gating of NMDA receptor function, a mechanism linking synaptic signaling dynamics to network excitability and cognition.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128718,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":580030,"name":"Thomas K. Creson","orcid":null,"position":1,"is_corresponding":false},{"id":300766,"name":"Camilo Rojas","orcid":"0000-0003-2453-1730","position":2,"is_corresponding":false},{"id":579417,"name":"Sabyasachi Maity","orcid":"0000-0003-4180-5983","position":3,"is_corresponding":false},{"id":579418,"name":"Aliza A. Le","orcid":"0000-0002-9155-0838","position":4,"is_corresponding":false},{"id":579419,"name":"Julie C. Lauterborn","orcid":"0000-0002-8444-6151","position":5,"is_corresponding":false},{"id":341754,"name":"Brent Wilkinson","orcid":"0000-0001-7852-1218","position":6,"is_corresponding":false},{"id":579420,"name":"Nicolas Hartel","orcid":"0000-0001-6191-9975","position":7,"is_corresponding":false},{"id":461181,"name":"Nicholas A. Graham","orcid":"0000-0002-6811-1941","position":8,"is_corresponding":false},{"id":134875,"name":"Adrian Reich","orcid":"0000-0002-1680-8659","position":9,"is_corresponding":false},{"id":321428,"name":"Gemma Gou","orcid":"0000-0001-7438-2417","position":10,"is_corresponding":false},{"id":275414,"name":"Yoichi Araki","orcid":"0000-0002-3455-9377","position":11,"is_corresponding":false},{"id":87271,"name":"Àlex Bayés","orcid":"0000-0002-5265-6306","position":12,"is_corresponding":false},{"id":341755,"name":"Marcelo P. Coba","orcid":"0000-0001-7075-6338","position":13,"is_corresponding":false},{"id":579421,"name":"Gary Lynch","orcid":"0000-0002-3520-8544","position":14,"is_corresponding":false},{"id":300768,"name":"Courtney A. Miller","orcid":"0000-0001-8628-4902","position":15,"is_corresponding":false},{"id":296428,"name":"Gavin Rumbaugh","orcid":"0000-0001-6360-3894","position":16,"is_corresponding":false},{"id":300764,"name":"Murat Kılınç","orcid":"0000-0003-0928-7573","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","pmid":null,"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":[]}