The muscle protein Dok-7 is essential for neuromuscular synaptogenesis
The muscle protein Dok-7 is essential for neuromuscular synaptogenesis
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DOI：
10.1126/science.1127142
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发表时间：
2006-06-23
期刊：
影响因子：
56.9
通讯作者：
Yamanashi, Yuji
中科院分区：
文献类型：
--
作者：
Okada, Kumiko;Inoue, Akane;Yamanashi, Yuji
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。在神经支配后，神经聚集蛋白激活MuSK以建立突触后装置，尽管神经肌肉突触的聚集蛋白非依赖性形成也可以在没有神经传递的情况下实验性地发生。Dok-7是一种与MuSK相互作用的胞质蛋白，对培养的肌管中的MuSK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的相互作用对神经肌肉突触发生至关重要。
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.