The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo
The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo
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DOI：
10.1016/s0092-8674(00)81251-9
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发表时间：
1996-05-17
期刊：
影响因子：
64.5
通讯作者：
Yancopoulos, GD
中科院分区：
文献类型：
--
作者：
DeChiara, TM;Bowen, DC;Yancopoulos, GD
神经肌肉突触的形成需要生长的运动轴突和分化的肌肉细胞之间的一系列诱导相互作用，最终在高度特化的神经末梢与突触后肌肉表面上的复杂分子结构的精确并置中达到高潮。介导这些诱导相互作用的受体和信号通路尚不清楚。我们已经产生了对编码MuSK的基因进行靶向破坏的小鼠，MuSK是一种选择性定位于突触后肌肉表面的受体酪氨酸激酶。神经肌肉突触在这些小鼠中不形成，表明突触形成诱导失败。连同随附手稿的结果，我们的研究结果表明MuSK对关键的神经源性信号（聚集蛋白）做出反应，进而激活负责突触形成各个方面的信号级联，包括突触后膜的组织、突触特异性转录和突触前分化。
Formation of neuromuscular synapses requires a series of inductive interactions between growing motor axons and differentiating muscle cells, culminating in the precise juxtaposition of a highly specialized nerve terminal with a complex molecular structure on the postsynaptic muscle surface. The receptors and signaling pathways mediating these inductive interactions are not known. We have generated mice with a targeted disruption of the gene encoding MuSK, a receptor tyrosine kinase selectively localized to the postsynaptic muscle surface. Neuromuscular synapses do not form in these mice, suggesting a failure in the induction of synapse formation. Together with the results of an accompanying manuscript, our findings indicate that MuSK responds to a critical nerve-derived signal (agrin), and in turn activates signaling cascades responsible for all aspects of synapse formation, including organization of the postsynaptic membrane, synapse-specific transcription, and presynaptic differentiation.