{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:25:15Z","timestamp":1791498315687,"version":"4.3.4"},"reference-count":70,"publisher":"Society for Neuroscience","issue":"38","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":218,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2018,9,19]]},"abstract":"<jats:p>\n                    Action potential-evoked neurotransmitter release is impaired in knock-out neurons lacking synaptic cell-adhesion molecules \u03b1-neurexins (\u03b1Nrxns), the extracellularly longer variants of the three vertebrate\n                    <jats:italic>Nrxn<\/jats:italic>\n                    genes. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through presynaptic high-voltage gated calcium channels like the ubiquitous P\/Q-type (Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1) triggers release of fusion-ready vesicles at many boutons. \u03b12\u03b4 Auxiliary subunits regulate trafficking and kinetic properties of Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1 pore-forming subunits but it has remained unclear if this involves \u03b1Nrxns. Using live cell imaging with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    indicators, we report here that the total presynaptic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx in primary hippocampal neurons of \u03b1Nrxn triple knock-out mice of both sexes is reduced and involved lower Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1-mediated transients. This defect is accompanied by lower vesicle release, reduced synaptic abundance of Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1 pore-forming subunits, and elevated surface mobility of \u03b12\u03b4-1 on axons. Overexpression of Nrxn1\u03b1 in \u03b1Nrxn triple knock-out neurons is sufficient to restore normal presynaptic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and synaptic vesicle release. Moreover, coexpression of Nrxn1\u03b1 together with \u03b12\u03b4-1 subunits facilitates Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx further but causes little augmentation together with a different subunit, \u03b12\u03b4-3, suggesting remarkable specificity. Expression of defined recombinant Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1 channels in heterologous cells validates and extends the findings from neurons. Whole-cell patch-clamp recordings show that Nrxn1\u03b1 in combination with \u03b12\u03b4-1, but not with \u03b12\u03b4-3, facilitates Ca\n                    <jats:sup>2+<\/jats:sup>\n                    currents of recombinant Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1 without altering channel kinetics. These results suggest that presynaptic Nrxn1\u03b1 acts as a positive regulator of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.1 channels containing \u03b12\u03b4-1 subunits. We propose that this regulation represents an important way for neurons to adjust synaptic strength.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Synaptic transmission between neurons depends on the fusion of neurotransmitter-filled vesicles with the presynaptic membrane, which subsequently activates postsynaptic receptors. Influx of calcium ions into the presynaptic terminal is the key step to trigger vesicle release and involves different subtypes of voltage-gated calcium channels. We study the regulation of calcium channels by neurexins, a family of synaptic cell-adhesion molecules that are essential for many synapse properties. Using optical measurements of calcium influx in cultured neurons and electrophysiological recordings of calcium currents from recombinant channels, we show that a major neurexin variant facilitates calcium influx through P\/Q-type channels by interacting with their \u03b12\u03b4-1 auxiliary subunits. These results propose a novel way how neurons can modulate the strength of distinct synapses.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0511-18.2018","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T13:47:19Z","timestamp":1534168039000},"page":"8277-8294","source":"Crossref","is-referenced-by-count":87,"title":["\u03b1-Neurexins Together with \u03b12\u03b4-1 Auxiliary Subunits Regulate Ca\n                    <sup>2+<\/sup>\n                    Influx through Ca\n                    <sub>v<\/sub>\n                    2.1 Channels"],"prefix":"10.1523","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-5850","authenticated-orcid":false,"given":"Johannes","family":"Brockhaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schreitm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Repetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Klatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-9971","authenticated-orcid":false,"given":"Carsten","family":"Reissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2988-4482","authenticated-orcid":false,"given":"Keith","family":"Elmslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Heine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-984X","authenticated-orcid":false,"given":"Markus","family":"Missler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2018,8,13]]},"reference":[{"key":"2023041803324742000_38.38.8277.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.056"},{"key":"2023041803324742000_38.38.8277.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.060"},{"key":"2023041803324742000_38.38.8277.3","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4024"},{"key":"2023041803324742000_38.38.8277.4","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2015.00003"},{"key":"2023041803324742000_38.38.8277.5","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2461"},{"key":"2023041803324742000_38.38.8277.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.10.002"},{"key":"2023041803324742000_38.38.8277.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504183102"},{"key":"2023041803324742000_38.38.8277.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.07.014"},{"key":"2023041803324742000_38.38.8277.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403731111"},{"key":"2023041803324742000_38.38.8277.10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"2023041803324742000_38.38.8277.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.04.011"},{"key":"2023041803324742000_38.38.8277.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"2023041803324742000_38.38.8277.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1572-13.2014"},{"key":"2023041803324742000_38.38.8277.14","doi-asserted-by":"publisher","DOI":"10.1038\/nn1074"},{"key":"2023041803324742000_38.38.8277.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.01.010"},{"key":"2023041803324742000_38.38.8277.16","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3311"},{"key":"2023041803324742000_38.38.8277.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1913-06.2006"},{"key":"2023041803324742000_38.38.8277.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.2458626"},{"key":"2023041803324742000_38.38.8277.19","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3563"},{"key":"2023041803324742000_38.38.8277.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.025"},{"key":"2023041803324742000_38.38.8277.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910297106"},{"key":"2023041803324742000_38.38.8277.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-18-06884.1997"},{"key":"2023041803324742000_38.38.8277.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00172-1"},{"key":"2023041803324742000_38.38.8277.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.06.028"},{"key":"2023041803324742000_38.38.8277.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1705"},{"key":"2023041803324742000_38.38.8277.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.064"},{"key":"2023041803324742000_38.38.8277.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.035"},{"key":"2023041803324742000_38.38.8277.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605256113"},{"key":"2023041803324742000_38.38.8277.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3349-07.2007"},{"key":"2023041803324742000_38.38.8277.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.07.021"},{"key":"2023041803324742000_38.38.8277.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708930105"},{"key":"2023041803324742000_38.38.8277.32","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3137"},{"key":"2023041803324742000_38.38.8277.33","doi-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