| First Author | Bolliger MF | Year | 2010 |
| Journal | J Cell Sci | Volume | 123 |
| Issue | Pt 22 | Pages | 3944-55 |
| PubMed ID | 20980386 | Mgi Jnum | J:182912 |
| Mgi Id | MGI:5317074 | Doi | 10.1242/jcs.072090 |
| Citation | Bolliger MF, et al. (2010) Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction. J Cell Sci 123(Pt 22):3944-55 |
| abstractText | 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 alpha- and beta-sites by an as-yet-unspecified protease as a regulatory access for relieving the agrin-dependent constraint on endplate reorganization during NMJ maturation. |
