{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:00:46Z","timestamp":1791104446023,"version":"4.1.0"},"reference-count":29,"publisher":"The Company of Biologists","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:p>During the initial stage of neuromuscular junction (NMJ) formation, nerve-derived agrin cooperates with muscle-autonomous mechanisms in the organization and stabilization of a plaque-like postsynaptic specialization at the site of nerve\u2013muscle contact. Subsequent NMJ maturation to the characteristic pretzel-like appearance requires extensive structural reorganization. We found that the progress of plaque-to-pretzel maturation is regulated by agrin. Excessive cleavage of agrin via transgenic overexpression of an agrin-cleaving protease, neurotrypsin, in motoneurons resulted in excessive reorganizational activity of the NMJs, leading to rapid dispersal of the synaptic specialization. By contrast, expression of cleavage-resistant agrin in motoneurons slowed down NMJ remodeling and delayed NMJ maturation. Neurotrypsin, which is the sole agrin-cleaving protease in the CNS, was excluded as the physiological agrin-cleaving protease at the NMJ, because NMJ maturation was normal in neurotrypsin-deficient mice. Together, our analyses characterize agrin cleavage at its proteolytic \u03b1- and \u03b2-sites by an as-yet-unspecified protease as a regulatory access for relieving the agrin-dependent constraint on endplate reorganization during NMJ maturation.<\/jats:p>","DOI":"10.1242\/jcs.072090","type":"journal-article","created":{"date-parts":[[2010,10,28]],"date-time":"2010-10-28T02:04:25Z","timestamp":1288231465000},"page":"3944-3955","source":"Crossref","is-referenced-by-count":95,"title":["Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction"],"prefix":"10.1242","volume":"123","author":[{"given":"Marc F.","family":"Bolliger","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zurlinden","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Zurich, 8057 Zurich, 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