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The formation of the neuromuscular synapse requires muscle-specificreceptor kinase (MuSK) to orchestrate postsynaptic differentiation,including the clustering of receptors for the neurotransmitteracetylcholine. Upon innervation, neural agrin activates MuSKto establish the postsynaptic apparatus, although agrin-independentformation of neuromuscular synapses can also occur experimentallyin the absence of neurotransmission. Dok-7, a MuSK-interactingcytoplasmic protein, is essential for MuSK activation in culturedmyotubes; in particular, the Dok-7 phosphotyrosine-binding domainand its target in MuSK are indispensable. Mice lacking Dok-7formed neither acetylcholine receptor clusters nor neuromuscularsynapses. Thus, Dok-7 is essential for neuromuscular synaptogenesisthrough its interaction with MuSK.
1 Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113–8510, Japan. 2 School of Biomedical Science, Tokyo Medical and Dental University, Tokyo 113–8510, Japan. 3 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108–8639, Japan. 4 Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113–0032, Japan. 5 The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852–8501, Japan.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: yamanashi.creg{at}mri.tmd.ac.jp (Y.Y.); higuchi.creg{at}mri.tmd.ac.jp (O.H.)
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