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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,3,28]]},"abstract":"<jats:p>\n                    \u03b1- and \u03b2-neurexins are extensively alternatively spliced, presynaptic cell-adhesion molecules that are thought to organize synapse assembly. However, recent data revealed that, in the hippocampus in\u00a0vivo, the deletion of one neurexin isoform,\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    , surprisingly increased excitatory synapse numbers and enhanced their presynaptic release probability, suggesting that\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    restricts, instead of enabling, synapse assembly. To delineate the synaptic function and mechanism of action of\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    , we examined cultured hippocampal neurons as a reduced system. In heterologous synapse formation assays, different alternatively spliced Nrxn2\u03b2 isoforms robustly promoted synapse assembly similar to Nrxn1\u03b2 and Nrxn3\u03b2, consistent with a general synaptogenic function of neurexins. Deletion of\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    from cultured hippocampal neurons, however, caused a significant increase in synapse density and release probability, replicating the in\u00a0vivo data that suggested a synapse-restricting function. Rescue experiments revealed that two of the four Nrxn2\u03b2 splice variants (Nrxn2\u03b2-SS4+\/SS5\u2212 and Nrxn2\u03b2-SS4+\/SS5+) reversed the increase in synapse density in\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    -deficient neurons, whereas only one of the four Nrxn2\u03b2 splice variants (Nrxn2\u03b2-SS4+\/SS5+) normalized the increase in release probability in\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    -deficient neurons. Thus, a subset of\n                    <jats:italic>Nrxn2<\/jats:italic>\n                    splice variants restricts synapse numbers and restrains their release probability in cultured neurons.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2300363120","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T14:12:19Z","timestamp":1679667139000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["RETRACTED: Neurexin-2 restricts synapse numbers and restrains the presynaptic release probability by an alternative splicing-dependent mechanism"],"prefix":"10.1073","volume":"120","author":[{"given":"Pei-Yi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu 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