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The muscle protein Dok-7 is essential for neuromuscular synaptogenesis
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Okada, Kumiko
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机构: Tokyo Med & Dent Univ, Inst Med Res, Dept Cell Regulat, Tokyo 1138510, Japan

Inoue, Akane
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机构: Tokyo Med & Dent Univ, Inst Med Res, Dept Cell Regulat, Tokyo 1138510, Japan

Okada, Momoko
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Murata, Yoji
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Jigami, Takafumi
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Kubo, Sachiko
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Shiraishi, Hirokazu
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Eguchi, Katsumi
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Motomura, Masakatsu
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Akiyama, Tetsu
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Iwakura, Yoichiro
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Higuchi, Osamu
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Tokyo Med & Dent Univ, Inst Med Res, Dept Cell Regulat, Tokyo 1138510, Japan Tokyo Med & Dent Univ, Inst Med Res, Dept Cell Regulat, Tokyo 1138510, Japan

Yamanashi, Yuji
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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
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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.
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页码:1802 / 1805
页数:4
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