| First Author | Inoue A | Year | 2009 |
| Journal | Sci Signal | Volume | 2 |
| Issue | 59 | Pages | ra7 |
| PubMed ID | 19244212 | Mgi Jnum | J:260261 |
| Mgi Id | MGI:6140656 | Doi | 10.1126/scisignal.2000113 |
| Citation | Inoue A, et al. (2009) Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation. Sci Signal 2(59):ra7 |
| abstractText | The formation of the neuromuscular junction (NMJ) is orchestrated by the muscle-specific receptor tyrosine kinase MuSK and by neural agrin, an extracellular activator of MuSK. We previously showed that the MuSK-interacting protein Dok-7 is essential for neuromuscular synaptogenesis, although the mechanisms by which Dok-7 regulates MuSK activity and promotes synapse formation have been unclear. Here, we show that Dok-7 directly interacts with the cytoplasmic portion of MuSK and activates the receptor tyrosine kinase, and that neural agrin requires Dok-7 to activate MuSK. In vivo overexpression of Dok-7 increased MuSK activation and promoted NMJ formation. Furthermore, Dok-7 was required for the localization of MuSK in the central region of muscle, which is essential for the correct formation of NMJs in this region. These observations indicate that Dok-7 positively regulates neuromuscular synaptogenesis by controlling MuSK activity, its distribution, and its responsiveness to neural agrin. |
