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
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Science. 2006 Jun 23;312(5781):1802-5. doi: 10.1126/science.1127142.
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.
神经肌肉突触的形成需要肌肉特异性受体激酶（MuSK）来协调突触后分化，包括神经递质乙酰胆碱受体的聚集。在神经支配时，神经聚集蛋白激活MuSK以建立突触后装置，尽管在没有神经传递的情况下，神经肌肉突触的非聚集蛋白依赖性形成也可通过实验发生。Dok-7是一种与MuSK相互作用的细胞质蛋白，对于培养的肌管中MuSK的激活至关重要；特别是，Dok-7磷酸酪氨酸结合结构域及其在MuSK中的靶点是不可或缺的。缺乏Dok-7的小鼠既不形成乙酰胆碱受体簇，也不形成神经肌肉突触。因此，Dok-7通过与MuSK相互作用对神经肌肉突触形成至关重要。
