The muscle protein Dok-7 is essential for neuromuscular synaptogenesis |
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| Authors: | Okada Kumiko Inoue Akane Okada Momoko Murata Yoji Kakuta Shigeru Jigami Takafumi Kubo Sachiko Shiraishi Hirokazu Eguchi Katsumi Motomura Masakatsu Akiyama Tetsu Iwakura Yoichiro Higuchi Osamu Yamanashi Yuji |
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| Institution: | Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. |
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| Abstract: | The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK. |
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