{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:56:51Z","timestamp":1785405411201,"version":"3.56.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the NIH","doi-asserted-by":"publisher","award":["R56NS128048"],"award-info":[{"award-number":["R56NS128048"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1122351"],"award-info":[{"award-number":["APP1122351"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007567","name":"City University of Hong Kong","doi-asserted-by":"publisher","award":["9610647"],"award-info":[{"award-number":["9610647"]}],"id":[{"id":"10.13039\/100007567","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:p>\n                    Neurotransmitter release at the\n                    <jats:italic toggle=\"yes\">Caenorhabditis elegans<\/jats:italic>\n                    neuromuscular junction is governed by a dual Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensor system composed of SNT-1 and SNT-3, which function analogously to the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensor systems found in certain mammalian neurons, such as synaptotagmin-1 and -7 (Syt1\/Syt7) in the hippocampus. In this study, we investigated how SNT-1 and SNT-3 mediate fast and slow neurotransmitter release through their potential interactions with the SNARE complex and their polybasic motifs. AlphaFold 3 models of SNT-1\u2013SNARE and SNT-3\u2013SNARE complexes predicted a C2B\u2013SNARE arrangement consistent with the canonical Syt1\u2013SNARE primary interface [Zhou\n                    <jats:italic toggle=\"yes\">et al.<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Nature<\/jats:italic>\n                    <jats:bold>525<\/jats:bold>\n                    , 62\u201367 (2015)] and precisely identified conserved binding residues within the C2B domains, as well as in SNAP-25 and Syntaxin, highlighting the evolutionary conservation of this interaction. Electrophysiological analyses using targeted mutagenesis demonstrated that both SNT-1 and SNT-3 require C2B\u2013SNARE interactions and polybasic motifs within their C2 domains to drive evoked fast and slow neurotransmitter release. Notably, SNT-1 and SNT-3 exhibited differential dependence on distinct regions of the C2B\u2013SNARE interface and their respective polybasic motifs, suggesting that Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -triggered fast and slow release operate via distinct mechanistic strategies. Furthermore, we found that SNT-1 mediates spontaneous neurotransmitter release through multiple pathways, involving not only the primary C2B\u2013SNARE interface but also additional putative SNARE-binding interactions. Together, our findings uncover both conserved and divergent mechanisms for synaptic exocytosis regulated by the dual Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sensors in\n                    <jats:italic toggle=\"yes\">C. elegans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.2532992123","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:09:31Z","timestamp":1781806171000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Evolutionarily conserved and divergent mechanisms of dual Ca\n                    <sup>2+<\/sup>\n                    sensors in synaptic vesicle exocytosis"],"prefix":"10.1073","volume":"123","author":[{"given":"Lei","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03q8dnn23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, City 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