{"doi":"10.1371/journal.pbio.3003023","title":"The exocytosis regulator complexin controls spontaneous synaptic vesicle release in a CAPS-dependent manner at C. elegans excitatory synapses","abstract":"The balance between synaptic excitation and inhibition (E/I) is essential for coordinating motor behavior, yet the differential roles of exocytosis regulators in this balance are less understood. In this study, we investigated the roles of 2 conserved exocytosis regulators, complexin/CPX-1 and CAPS/UNC-31, in excitatory versus inhibitory synapses at Caenorhabditis elegans neuromuscular junctions. cpx-1 null mutants exhibited a marked increase in spontaneous release specifically at excitatory synapses, alongside an unequal reduction in excitatory and inhibitory evoked release. A clamping-specific knockin mutant, cpx-1(Δ12), which preserved evoked release, also showed a biased enhancement in excitatory spontaneous release. Conversely, the unc-31 null mutation, while maintaining normal spontaneous release, displayed a more pronounced reduction in evoked release at excitatory synapses. Notably, we found that CPX-1's clamping function is dependent on UNC-31 and is sensitive to external Ca2+. Pull-down experiments confirmed that CAPS/UNC-31 does not directly interact with complexin, implying an indirect regulatory mechanism. Moreover, complexin regulates activity-dependent synaptic plasticity, which is also UNC-31 dependent. The unexpected role of CAPS/UNC-31 in the absence of CPX-1 clamping function may underpin the synaptic E/I balance and coordinated behavioral outputs in different species.","journal":"PLoS Biology","year":2025,"id":537957,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":1190886,"name":"Chun Hin Chow","orcid":null,"position":1,"is_corresponding":false},{"id":1424163,"name":"Yu Zhang","orcid":"0000-0001-8660-331X","position":2,"is_corresponding":false},{"id":362498,"name":"Mengjia Huang","orcid":null,"position":3,"is_corresponding":false},{"id":1191363,"name":"Randa Higazy","orcid":null,"position":4,"is_corresponding":false},{"id":1191364,"name":"Neeraja Ramakrishnan","orcid":null,"position":5,"is_corresponding":false},{"id":550618,"name":"Lili Chen","orcid":"0000-0002-9965-8990","position":6,"is_corresponding":false},{"id":1235232,"name":"Xuhui Chen","orcid":"0000-0002-9791-2051","position":7,"is_corresponding":false},{"id":627924,"name":"Yixiang Deng","orcid":"0000-0002-4771-8058","position":8,"is_corresponding":false},{"id":711995,"name":"Sheng Wang","orcid":"0000-0002-2096-2616","position":9,"is_corresponding":false},{"id":990225,"name":"Cuntai Zhang","orcid":"0000-0002-2365-5646","position":10,"is_corresponding":false},{"id":1405499,"name":"Cong Ma","orcid":"0000-0002-7814-0500","position":11,"is_corresponding":false},{"id":360553,"name":"Shuzo Sugita","orcid":"0000-0002-9182-873X","position":12,"is_corresponding":false},{"id":360552,"name":"Shangbang Gao","orcid":"0000-0001-5431-4628","position":13,"is_corresponding":false},{"id":752376,"name":"Ya Wang","orcid":"0000-0001-6229-4495","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39913617","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":[]}