{"doi":"10.1073/pnas.2514151122","title":"Monoamine-induced diacylglycerol signaling rapidly accumulates Unc13 in nanoclusters for fast presynaptic potentiation","abstract":"neuromuscular junction, we show that octopamine, the invertebrate analog of norepinephrine, potentiates evoked neurotransmitter release on the timescale of one minute via a G-protein-coupled pathway involving presynaptic OAMB receptors and phospholipase C. This fast potentiation correlates with elevated signals of the release factor Unc13A and the scaffolding protein Bruchpilot. Live, single-molecule imaging of endogenously tagged Unc13 revealed its instantly reduced motility and increased concentration in synaptic nanoclusters with potentiation. Presynaptic knockdown of Unc13A fully blocked fast potentiation. Moreover, deleting its N-terminal localization sequence mislocalized the protein fragment to the cytosol, but still allowed for rapid plasma membrane recruitment by diacylglycerol (DAG) analog phorbol esters and octopamine, implicating a role of more C-terminal domains. A point mutation of endogenous Unc13 in its DAG-binding C1 domain blocked plasticity-induced nanoscopic enrichment and synaptic potentiation. The mutation increased basal neurotransmission but reduced Unc13 levels, revealing a gain of function and potential homeostatic compensation. The mutation also blocked phorbol ester-induced potentiation, decreased the calcium sensitivity of neurotransmission, and caused short-term synaptic depression. Homeostatic potentiation induced by postsynaptic receptor block mirrored octopamine-induced Unc13 recruitment and required presynaptic OAMB receptors, indicating overlapping machinery. Thus, rapid Unc13 immobilization and nanoscale compaction are salient features of fast presynaptic potentiation.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":524217,"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":0.9513,"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":1030700,"name":"Tina Ghelani","orcid":"0000-0003-1835-4686","position":1,"is_corresponding":false},{"id":1397732,"name":"Torsten Götz","orcid":"0000-0002-5894-1474","position":2,"is_corresponding":false},{"id":474085,"name":"Keagan S. Chronister","orcid":null,"position":3,"is_corresponding":false},{"id":251975,"name":"Mercedes Bengochea","orcid":"0000-0002-6446-5021","position":4,"is_corresponding":false},{"id":1397733,"name":"Livia Ceresnova","orcid":"0009-0005-1556-0582","position":5,"is_corresponding":false},{"id":955023,"name":"Christian Christensen","orcid":"0000-0003-0550-4948","position":6,"is_corresponding":false},{"id":939073,"name":"Thiago C. Moulin","orcid":"0000-0001-7811-5383","position":7,"is_corresponding":false},{"id":1397734,"name":"Hanna Kern","orcid":"0000-0001-7505-7130","position":8,"is_corresponding":false},{"id":764552,"name":"Ulrich Thomas","orcid":"0000-0002-4372-8611","position":9,"is_corresponding":false},{"id":539478,"name":"Martin Heine","orcid":"0000-0002-0886-3113","position":10,"is_corresponding":false},{"id":212812,"name":"Stephan J. Sigrist","orcid":"0000-0002-1698-5815","position":11,"is_corresponding":false},{"id":317270,"name":"Alexander M. Walter","orcid":"0000-0001-5646-4750","position":12,"is_corresponding":false},{"id":1397731,"name":"Natalie Blaum","orcid":"0000-0002-3687-9059","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"40833403","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":[]}