Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39952
Bolliger, M F; Zurlinden, A; Lüscher, D; Bütikofer, L; Shakhova, O; Francolini, M; Kozlov, S V; Cinelli, P; Stephan, A; Kistler, A D; Rülicke, T; Pelczar, P; Ledermann, B; Fumagalli, G; Gloor, S M; Kunz, B; Sonderegger, P (2010). Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction. Journal of Cell Science, 123(Pt 22):3944-3955.
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-muscle 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 α- and β-sites by an as-yet-unspecified protease as a regulatory access for relieving the agrin-dependent constraint on endplate reorganization during NMJ maturation.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Biochemistry|
07 Faculty of Science > Institute of Biochemistry
05 Vetsuisse Faculty > Institute of Laboratory Animal Science
04 Faculty of Medicine > Institute of Laboratory Animal Science
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||21 Jan 2011 14:56|
|Last Modified:||27 Jan 2014 06:46|
|Publisher:||Company of Biologists|
|Citations:||Web of Science®. Times Cited: 18|
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