生物谷報(bào)道：神經(jīng)肌肉接頭的發(fā)育研究近年來有一系列重大突破,，集中于MuSK信號的研究上,。在昨天剛剛出版的Science上報(bào)道了日本長崎大學(xué)科學(xué)家Yuji Yamanashi最新的研究成果。神經(jīng)肌肉突觸發(fā)育要求肌肉特異性受體蛋白激酶（MuSK）信號,，調(diào)節(jié)突觸后的分化,，包括膽神經(jīng)遞質(zhì)乙酰膽堿受體的聚集等。而新發(fā)現(xiàn)的Dok-7蛋白,，在細(xì)胞漿內(nèi)與MuSK結(jié)合,，它們相互結(jié)合是活化肌管所必需的。Dok-7磷酸化結(jié)合的結(jié)構(gòu)域與MuSK結(jié)合位點(diǎn)是獨(dú)立的,。當(dāng)小鼠敲除Dok-7后,，不能形成神經(jīng)骨肉突觸和乙酰膽堿受體的聚集。因此Dok-7是神經(jīng)肌肉突觸發(fā)生中的必需因子,。
原始出處：
Kumiko Okada,1* Akane Inoue,1* Momoko Okada,1 Yoji Murata,1 Shigeru Kakuta,3 Takafumi Jigami,4 Sachiko Kubo,3 Hirokazu Shiraishi,5 Katsumi Eguchi,5 Masakatsu Motomura,5 Tetsu Akiyama,4 Yoichiro Iwakura,3 Osamu Higuchi,1 Yuji Yamanashi1. The Muscle Protein Dok-7 Is Essential for Neuromuscular Synaptogenesis . Science 23 June 2006: Vol. 312. no. 5781, pp. 1802 - 1805
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.
