In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 2, No. 59 ( 2009-02-24)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.2000113
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2009