The muscle protein Dok-7 is essential for neuromuscular synaptogenesis

被引:324
作者
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 [1 ]
Yamanashi, Yuji
机构
[1] Tokyo Med & Dent Univ, Inst Med Res, Dept Cell Regulat, Tokyo 1138510, Japan
[2] Tokyo Med & Dent Univ, Sch Biomed Sci, Tokyo 1138510, Japan
[3] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan
[4] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Mol & Genet Informat, Tokyo 1130032, Japan
[5] Nagasaki Univ, Grad Sch Biomed Sci, Dept Internal Med 1, Nagasaki 8528501, Japan
关键词
D O I
10.1126/science.1127142
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1802 / 1805
页数:4
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