{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:52:16Z","timestamp":1791121936072,"version":"4.1.0"},"reference-count":85,"publisher":"Society for Neuroscience","issue":"2","license":[{"start":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T00:00:00Z","timestamp":1310428800000},"content-version":"vor","delay-in-days":181,"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":[[2011,1,12]]},"abstract":"<jats:p>Synapse formation requires the organization of presynaptic active zones, the synaptic vesicle release sites, in precise apposition to postsynaptic neurotransmitter receptor clusters; however, the molecular mechanisms responsible for these processes remain unclear. Here, we show that P\/Q-type and N-type voltage-dependent calcium channels (VDCCs) play essential roles as scaffolding proteins in the organization of presynaptic active zones. The neuromuscular junction of double knock-out mice for P\/Q- and N-type VDCCs displayed a normal size but had significantly reduced numbers of active zones and docked vesicles and featured an attenuation of the active-zone proteins Bassoon, Piccolo, and CAST\/Erc2. Consistent with this phenotype, direct interactions of the VDCC \u03b21b or \u03b24 subunits and the active zone-specific proteins Bassoon or CAST\/Erc2 were confirmed by immunoprecipitation. A decrease in the number of active zones caused by a loss of presynaptic VDCCs resembled the pathological conditions observed in the autoimmune neuromuscular disorder Lambert\u2013Eaton myasthenic syndrome. At the synaptic cleft of double knock-out mice, we also observed a decrease of the synaptic organizer laminin \u03b22 protein, an extracellular ligand of P\/Q- and N-type VDCCs. However, the transcription level of laminin \u03b22 did not decrease in double knock-out mice, suggesting that the synaptic accumulation of laminin \u03b22 protein required its interaction with presynaptic VDCCs. These results suggest that presynaptic VDCCs link the target-derived synapse organizer laminin \u03b22 to active-zone proteins and function as scaffolding proteins to anchor active-zone proteins to the presynaptic membrane.<\/jats:p>","DOI":"10.1523\/jneurosci.3771-10.2011","type":"journal-article","created":{"date-parts":[[2011,1,12]],"date-time":"2011-01-12T17:23:23Z","timestamp":1294853003000},"page":"512-525","source":"Crossref","is-referenced-by-count":93,"title":["Calcium Channels Link the Muscle-Derived Synapse Organizer Laminin \u03b22 to Bassoon and CAST\/Erc2 to Organize Presynaptic Active Zones"],"prefix":"10.1523","volume":"31","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Billings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nishimune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,1,12]]},"reference":[{"key":"2023041303481788000_31.2.512.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.503"},{"key":"2023041303481788000_31.2.512.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611003104"},{"key":"2023041303481788000_31.2.512.3","doi-asserted-by":"publisher","DOI":"10.1038\/22768"},{"key":"2023041303481788000_31.2.512.4","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3640fje"},{"key":"2023041303481788000_31.2.512.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80520-6"},{"key":"2023041303481788000_31.2.512.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80881-8"},{"key":"2023041303481788000_31.2.512.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2006.01706.x"},{"key":"2023041303481788000_31.2.512.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06965.x"},{"key":"2023041303481788000_31.2.512.9","first-page":"214","article-title":"Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix","volume":"69","author":"Cases-Langhoff","year":"1996","journal-title":"Eur J Cell Biol"},{"key":"2023041303481788000_31.2.512.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.020"},{"key":"2023041303481788000_31.2.512.11","first-page":"2346","article-title":"Synaptic vesicles and pouches at the level of \u201cactive zones\u201d of the neuromuscular junction (in French)","volume":"271","author":"Couteaux","year":"1970","journal-title":"C R Acad Sci Hebd Seances Acad Sci D"},{"key":"2023041303481788000_31.2.512.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00086-2"},{"key":"2023041303481788000_31.2.512.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.025"},{"key":"2023041303481788000_31.2.512.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00190-4"},{"key":"2023041303481788000_31.2.512.15","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOBB.0000008033.02320.10"},{"key":"2023041303481788000_31.2.512.16","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200812150"},{"key":"2023041303481788000_31.2.512.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.24.7636"},{"key":"2023041303481788000_31.2.512.18","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220203"},{"key":"2023041303481788000_31.2.512.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.002"},{"key":"2023041303481788000_31.2.512.20","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1523\/JNEUROSCI.16-08-02488.1996","article-title":"CASK: a novel dlg\/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins","volume":"16","author":"Hata","year":"1996","journal-title":"J Neurosci"},{"key":"2023041303481788000_31.2.512.21","unstructured":"Haugland RP (2005) The handbook, a guide to fluorescent probes and labeling technologies (Invitrogen, Carlsbad, CA), Ed 10."},{"key":"2023041303481788000_31.2.512.22","doi-asserted-by":"publisher","DOI":"10.1038\/338229a0"},{"key":"2023041303481788000_31.2.512.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081089398"},{"key":"2023041303481788000_31.2.512.24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601468103"},{"key":"2023041303481788000_31.2.512.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15245"},{"key":"2023041303481788000_31.2.512.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05183.x"},{"key":"2023041303481788000_31.2.512.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.09.019"},{"key":"2023041303481788000_31.2.512.28","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880080213"},{"key":"2023041303481788000_31.2.512.29","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200411012"},{"key":"2023041303481788000_31.2.512.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1126308"},{"key":"2023041303481788000_31.2.512.31","doi-asserted-by":"publisher","DOI":"10.1038\/nn1904"},{"key":"2023041303481788000_31.2.512.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.033"},{"key":"2023041303481788000_31.2.512.33","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00210.2004"},{"key":"2023041303481788000_31.2.512.34","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2417"},{"key":"2023041303481788000_31.2.512.35","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90140-7"},{"key":"2023041303481788000_31.2.512.36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.1983.sp014943","article-title":"Antibodies to motor nerve terminals: an electrophysiological study of a human myasthenic syndrome transferred to mouse","volume":"344","author":"Lang","year":"1983","journal-title":"J Physiol"},{"key":"2023041303481788000_31.2.512.37","doi-asserted-by":"crossref","first-page":"9399","DOI":"10.1523\/JNEUROSCI.19-21-09399.1999","article-title":"Disruption of laminin \u03b22 chain production causes alterations in morphology and function in the CNS","volume":"19","author":"Libby","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303481788000_31.2.512.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.01.017"},{"key":"2023041303481788000_31.2.512.39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200712152"},{"key":"2023041303481788000_31.2.512.40","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi336"},{"key":"2023041303481788000_31.2.512.41","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1523\/JNEUROSCI.22-16-06939.2002","article-title":"Synaptic targeting of N-type calcium channels in hippocampal neurons","volume":"22","author":"Maximov","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303481788000_31.2.512.42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.35.24453"},{"key":"2023041303481788000_31.2.512.43","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02270"},{"key":"2023041303481788000_31.2.512.44","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01020-6"},{"key":"2023041303481788000_31.2.512.45","doi-asserted-by":"publisher","DOI":"10.1038\/nature01755"},{"key":"2023041303481788000_31.2.512.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.262787699"},{"key":"2023041303481788000_31.2.512.47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002307107"},{"key":"2023041303481788000_31.2.512.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005940107"},{"key":"2023041303481788000_31.2.512.49","doi-asserted-by":"publisher","DOI":"10.1038\/35046558"},{"key":"2023041303481788000_31.2.512.50","doi-asserted-by":"publisher","DOI":"10.1038\/nature03112"},{"key":"2023041303481788000_31.2.512.51","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20517"},{"key":"2023041303481788000_31.2.512.52","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200805095"},{"key":"2023041303481788000_31.2.512.53","doi-asserted-by":"publisher","DOI":"10.1038\/374258a0"},{"key":"2023041303481788000_31.2.512.54","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200202083"},{"key":"2023041303481788000_31.2.512.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.09.019"},{"key":"2023041303481788000_31.2.512.56","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.6.1507"},{"key":"2023041303481788000_31.2.512.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(99)00033-4"},{"key":"2023041303481788000_31.2.512.58","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/jnr.22282","article-title":"Selection of reference genes for real-time quantitative reverse transcription-polymerase chain reaction in hippocampal structure in a murine model of temporal lobe epilepsy with focal seizures","volume":"88","author":"Pernot","year":"2010","journal-title":"J Neurosci Res"},{"key":"2023041303481788000_31.2.512.59","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90682-0"},{"key":"2023041303481788000_31.2.512.60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.533ae.x"},{"key":"2023041303481788000_31.2.512.61","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.389"},{"key":"2023041303481788000_31.2.512.62","doi-asserted-by":"publisher","DOI":"10.1038\/35097557"},{"key":"2023041303481788000_31.2.512.63","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.102.2.420"},{"key":"2023041303481788000_31.2.512.64","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.4.1685"},{"key":"2023041303481788000_31.2.512.65","doi-asserted-by":"publisher","DOI":"10.1038\/415321a"},{"key":"2023041303481788000_31.2.512.66","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00207-1"},{"key":"2023041303481788000_31.2.512.67","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S59"},{"key":"2023041303481788000_31.2.512.68","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1773-07.2007"},{"key":"2023041303481788000_31.2.512.69","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1113\/jphysiol.1995.sp020865","article-title":"Decreased calcium currents in motor nerve terminals of mice with Lambert-Eaton myasthenic syndrome","volume":"487","author":"Smith","year":"1995","journal-title":"J Physiol"},{"key":"2023041303481788000_31.2.512.70","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200004000-00002"},{"key":"2023041303481788000_31.2.512.71","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307101"},{"key":"2023041303481788000_31.2.512.72","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.2.499"},{"key":"2023041303481788000_31.2.512.73","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408157"},{"key":"2023041303481788000_31.2.512.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.025"},{"key":"2023041303481788000_31.2.512.75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437991100"},{"key":"2023041303481788000_31.2.512.76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.101311"},{"key":"2023041303481788000_31.2.512.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.003"},{"key":"2023041303481788000_31.2.512.78","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.864"},{"key":"2023041303481788000_31.2.512.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.12.029"},{"key":"2023041303481788000_31.2.512.80","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1255-09.2009"},{"key":"2023041303481788000_31.2.512.81","doi-asserted-by":"publisher","DOI":"10.1038\/41580"},{"key":"2023041303481788000_31.2.512.82","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4978-04.2005"},{"key":"2023041303481788000_31.2.512.83","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00185-4"},{"key":"2023041303481788000_31.2.512.84","doi-asserted-by":"publisher","DOI":"10.1038\/43889"},{"key":"2023041303481788000_31.2.512.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.05.012"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3771-10.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:03:44Z","timestamp":1712102624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3771-10.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,12]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2011,1,12]]},"published-print":{"date-parts":[[2011,1,12]]}},"alternative-id":["10.1523\/JNEUROSCI.3771-10.2011"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3771-10.2011","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,12]]}}}