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Adv."],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>\n                    Synaptic transmission occurs synchronously with real-world events, far faster than vesicle fusion for hormone release or membrane biogenesis, all mediated by soluble\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -ethylmaleimide\u2013sensitive factor attachment protein receptor (SNARE) complexes. How SNAREs cooperate to achieve synchronous neurotransmitter release is a long-standing mystery. Rapid release (&lt;7 milliseconds) has been reconstituted from purified synaptic SNAREs, SNARE-assembling chaperones, and calcium ion sensors in a fully-defined, genetically validated system that enables single-molecule counting in docked vesicles before release. SNAREpin complexes (12\u00a0\u00b1\u00a00.3) are found in each such ready-release vesicle, suggesting a regular structure. Several genetic conditions (including point mutation of the synaptic vesicle protein Synaptophysin from a Synaptopathy patient and human and mouse disease mutations of the synaptic vesicle protein vesicle-associated membrane protein-2 (VAMP2) reduce the number of SNAREpins to 6\u00a0\u00b1\u00a00.3 and result in profoundly delayed release over 0.1 to 1 seconds. Omitting Synaptophysin, whose hexamers preassemble 12 copies of VAMP2, also yields ~6 SNAREpins and delays release.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea0592","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:59:22Z","timestamp":1782928762000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Turbocharging synaptic transmission: 12 SNAREpins are required for rapid release of reconstituted synaptic vesicles"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9297-8126","authenticated-orcid":true,"given":"Manindra","family":"Bera","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA."},{"name":"Nanobiology Institute, Yale University, West Haven, CT 06516, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atrouli","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA."},{"name":"Nanobiology Institute, Yale University, West Haven, CT 06516, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1689-1015","authenticated-orcid":true,"given":"Amit Koikkarah","family":"Aji","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA."},{"name":"Nanobiology Institute, Yale University, West Haven, CT 06516, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-9547","authenticated-orcid":true,"given":"Aniruddha","family":"Panda","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA."},{"name":"Nanobiology Institute, Yale University, West Haven, CT 06516, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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