生物谷报道：神经肌肉接头的发育研究近年来有一系列重大突破，集中于MuSK信号的研究上。在昨天刚刚出版的Science上报道了日本长崎大学科学家Yuji Yamanashi最新的研究成果。神经肌肉突触发育要求肌肉特异性受体蛋白激酶（MuSK）信号，调节突触后的分化，包括胆神经递质乙酰胆碱受体的聚集等。而新发现的Dok-7蛋白，在细胞浆内与MuSK结合，它们相互结合是活化肌管所必需的。Dok-7磷酸化结合的结构域与MuSK结合位点是独立的。当小鼠敲除Dok-7后，不能形成神经骨肉突触和乙酰胆碱受体的聚集。因此Dok-7是神经肌肉突触发生中的必需因子。
原始出处：
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.
