| First Author | Friese MB | Year | 2007 |
| Journal | Development | Volume | 134 |
| Issue | 23 | Pages | 4167-76 |
| PubMed ID | 17959719 | Mgi Jnum | J:128926 |
| Mgi Id | MGI:3768293 | Doi | 10.1242/dev.010702 |
| Citation | Friese MB, et al. (2007) Synaptic differentiation is defective in mice lacking acetylcholine receptor {beta}-subunit tyrosine phosphorylation. Development 134(23):4167-76 |
| abstractText | Agrin activates MuSK, a receptor tyrosine kinase expressed in skeletal muscle, leading to tyrosine phosphorylation of the acetylcholine receptor (AChR) beta-subunit and clustering of AChRs. The importance of AChR beta-subunit tyrosine phosphorylation in clustering AChRs and regulating synaptic differentiation is poorly understood. We generated mice with targeted mutations in the three intracellular tyrosines of the AChR beta-subunit (AChR-beta(3F/3F)). Mice lacking AChR beta-subunit tyrosine phosphorylation thrive postnatally and have no overt behavioral defects, indicating that AChR beta-subunit tyrosine phosphorylation is not essential for the formation of neuromuscular synapses. Nonetheless, the size of synapses and the density of synaptic AChRs are reduced in AChR- beta(3F/3F) mutant mice. Moreover, synapses are structurally simplified and the organization of postjunctional folds is aberrant in mice lacking tyrosine phosphorylation of the AChR beta-subunit. Furthermore, mutant AChRs cluster poorly in response to agrin and are readily extracted from the cell surface of cultured myotubes by non-ionic detergent. These data indicate that tyrosine phosphorylation of the AChR beta-subunit has an important role in organizing AChRs and regulating synaptic differentiation. |
