Details

Autor(en) / Beteiligte

• Bolliger, Marc F
• Zurlinden, Andreas
• Lüscher, Daniel
• Bütikofer, Lukas
• Shakhova, Olga
• Francolini, Maura
• Kozlov, Serguei V
• Cinelli, Paolo
• Stephan, Alexander
• Kistler, Andreas D
• Rülicke, Thomas
• Pelczar, Pawel
• Ledermann, Birgit
• Fumagalli, Guido
• Gloor, Sergio M
• Kunz, Beat
• Sonderegger, Peter

Titel

Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction

Ist Teil von

• Journal of cell science, 2010-11, Vol.123 (Pt 22), p.3944-3955

Ort / Verlag

England

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.