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Sci. Signal., 24 February 2009
Vol. 2, Issue 59, p. ra7
[DOI: 10.1126/scisignal.2000113]

RESEARCH ARTICLES

Editor's Summary

Extra Neuromuscular Junctions
At the neuromuscular junction (NMJ), the interface between muscle and nerve, clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane ensures efficient synaptic transmission. NMJ formation and AChR clustering require the muscle receptor tyrosine kinase MuSK and its extracellular activator, agrin. However, MuSK can cause NMJ formation in the absence of agrin, leading Inoue et al. to investigate the mechanisms by which MuSK is activated independently of agrin. They now show that the cytoplasmic protein Dok-7 can directly activate MuSK in vitro and in vivo and, when overexpressed in skeletal muscle, leads to the formation of NMJs with wider endplates and bearing more AChR clusters. Strikingly, agrin did not induce AChR clustering in myotubes from Dok-7–deficient mice unless Dok-7 was exogenously expressed, indicating that Dok-7 primes MuSK for subsequent further activation by agrin.

Citation: A. Inoue, K. Setoguchi, Y. Matsubara, K. Okada, N. Sato, Y. Iwakura, O. Higuchi, Y. Yamanashi, Dok-7 Activates the Muscle Receptor Kinase MuSK and Shapes Synapse Formation. Sci. Signal. 2, ra7 (2009).

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