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VDCCs interact extracellularly with the muscle\u2010derived synapse organizer, laminin \u03b22 and interact intracellularly with active zone\u2013specific proteins, such as Bassoon, CAST\/Erc2\/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P\/Q\u2010 and N\u2010type VDCCs double\u2010knockout mice, and they are consistent with the pathological conditions of Lambert\u2013Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin \u03b22 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies.<\/jats:p>","DOI":"10.1111\/j.1749-6632.2012.06836.x","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T19:02:49Z","timestamp":1355857369000},"page":"24-32","source":"Crossref","is-referenced-by-count":30,"title":["Active zones of mammalian neuromuscular junctions: formation, density, and aging"],"prefix":"10.1111","volume":"1274","author":[{"given":"Hiroshi","family":"Nishimune","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,17]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.533ae.x"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437991100"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.81.2.275"},{"key":"e_1_2_9_5_2","first-page":"2346","article-title":"Synaptic vesicles and pouches at the level of \u201cactive zones\u201d of the neuromuscular junction","volume":"271","author":"Couteaux R.","year":"1970","journal-title":"C R Acad. 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