{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:44:51Z","timestamp":1791182691629,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,1,29]],"date-time":"2008-01-29T00:00:00Z","timestamp":1201564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012654","name":"Olga Mayenfisch Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012654","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>\n                    The synaptic serine protease neurotryp sin is considered to be essential for the establishment and maintenance of cognitive brain functions, because humans lacking functional neurotrypsin suffer from severe mental retardation. Neurotrypsin cleaves agrin at two homologous sites, liberating a 90\u2010kDa and a C\u2010terminal 22\u2010kDa fragment from the N\u2010terminal moi ety of agrin. Morphological analyses indicate that neu rotrypsin is contained in presynaptic terminals and externalized in association with synaptic activity, while agrin is localized to the extracellular space at or in the vicinity of the synapse. Here, we present a detailed biochemical analysis of neurotrypsin\u2010mediated agrin cleavage in the murine brain. In brain homogenates, we found that neurotrypsin exclusively cleaves glycanated variants of agrin. Studies with isolated synaptosomes obtained by subcellular fractionation from brains of wild\u2010type and neurotrypsin\u2010overexpressing mice re vealed that neurotrypsin\u2010dependent cleavage of agrin was concentrated at synapses, where the most heavily glycanated variants of agrin predominate. Because agrin has been shown to play an important role in the formation and the maintenance of excitatory synapses in the central nervous system, its local cleavage at the synapse implicates the neurotrypsin\/agrin system in the regulation of adaptive reorganizations of the synaptic circuitry in the context of cognitive functions, such as learning and memory.\u2014 Stephan, A., Mateos, J. M., Kozlov, S. V., Cinelli, P., Kistler, A. D., Hettwer, S., Rulicke, T., Streit, P., Kunz, B., Sonderegger, P. Neu rotrypsin cleaves agrin locally at the synapse.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 1861\u20131873 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-100008","type":"journal-article","created":{"date-parts":[[2008,1,29]],"date-time":"2008-01-29T23:58:58Z","timestamp":1201651138000},"page":"1861-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Neurotrypsin cleaves agrin locally at the synapse"],"prefix":"10.1096","volume":"22","author":[{"given":"Alexander","family":"Stephan","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Mateos","sequence":"additional","affiliation":[{"name":"Brain Research Institute University of Zurich Zurich Switzerland"},{"name":"Neurotune AG Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serguei V.","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"},{"name":"Cancer and Developmental Biology Lab oratory National Cancer Institute Center for Cancer Re search Frederick MD 1702\u20101201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cinelli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"},{"name":"Institute of Laboratory Animal Science University of Zurich Winterthurerstrasse 190 CH\u20108057 Zu rich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas David","family":"Kistler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"},{"name":"University Hospital Zurich R\u00e4mistrasse 100 CH\u20108091 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hettwer","sequence":"additional","affiliation":[{"name":"Neurotune AG Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"R\u00fclicke","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science University of Zurich Zurich Switzerland"},{"name":"Institute of Laboratory Animal Science and Biomodels Austria University of Veterinary Medicine, Vienna Veterin\u00e4rplatz 1 A\u20101210 Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Streit","sequence":"additional","affiliation":[{"name":"Brain Research Institute University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Kunz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sonderegger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1997.0616"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076521"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(97)00205-4"},{"key":"e_1_2_7_5_1","article-title":"Activity\u2010induced synaptic capture and exocytosis of the neuronal serine protease neurotrypsin","author":"Frischknecht R.","year":"2007","journal-title":"J. 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