Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.

Luo ZG; Wang Q; Zhou JZ; Wang J; Luo Z; Liu M; He X; Wynshaw Boris A; Xiong WC; Lu B; Mei L

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Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.

机译：通过与MuSK和PAK1杂散相互作用来调控AChR聚类。

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An important aspect of synapse development is the clustering of neurotransmitter receptors in the postsynaptic membrane. Although MuSK is required for acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ), the underlying molecular mechanisms remain unclear. We report here that in muscle cells, MuSK interacts with Dishevelled (Dvl), a signaling molecule important for planar cell polarity. Disruption of the MuSK-Dvl interaction inhibits Agrin- and neuron-induced AChR clustering. Expression of dominant-negative Dvl1 in postsynaptic muscle cells reduces the amplitude of spontaneous synaptic currents at the NMJ. Moreover, Dvl1 interacts with downstream kinase PAK1. Agrin activates PAK, and this activation requires Dvl. Inhibition of PAK1 activity attenuates AChR clustering. These results demonstrate important roles of Dvl and PAK in Agrin/MuSK-induced AChR clustering and reveal a novel function of Dvl in synapse development.

机译：突触发展的一个重要方面是突触后膜中神经递质受体的聚集。尽管MuSK是在神经肌肉接头（NMJ）上乙酰胆碱受体（AChR）聚集所需的，但潜在的分子机制仍不清楚。我们在这里报告说，在肌肉细胞中，MuSK与Disheveled（Dvl）相互作用，后者对平面细胞极性很重要。 MuSK-Dvl相互作用的破坏抑制了Agrin和神经元诱导的AChR簇。突触后肌细胞中显性负性Dvl1的表达降低了NMJ处自发突触电流的幅度。此外，Dvl1与下游激酶PAK1相互作用。 Agrin激活PAK，并且此激活需要Dvl。 PAK1活性的抑制减弱AChR群集。这些结果证明了Dvl和PAK在Agrin / MuSK诱导的AChR簇中的重要作用，并揭示了Dvl在突触发育中的新功能。

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《Neuron》 |2002年第3期|共17页
作者
Luo ZG; Wang Q; Zhou JZ; Wang J; Luo Z; Liu M; He X; Wynshaw Boris A; Xiong WC; Lu B; Mei L;
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正文语种 eng
中图分类神经生理学;
关键词
Anterior Horn Cells; Muscle; Skeletal; Neuromuscular Junction; Phosphoproteins; 前角细胞; 肌; 骨骼; 神经肌肉接头; 磷蛋白类; 蛋白质丝氨酸苏氨酸激酶; 受体; 胆碱能;

机译：Anterior Horn Cells;Muscle;Skeletal;Neuromuscular Junction;Phosphoproteins;前角细胞;肌;骨骼;神经肌肉接头;磷蛋白类;蛋白质丝氨酸苏氨酸激酶;受体;胆碱能;

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专利

1. Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. [J] . Luo ZG, Wang Q, Zhou JZ, Neuron . 2002,第3期

机译：通过与MuSK和PAK1杂散相互作用来调控AChR聚类。
2. Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2. [J] . Waxman JS Developmental dynamics: an official publication of the American Association of Anatomists . 2005,第1期

机译：斑马鱼杂乱相互作用蛋白Dapper1和Dapper2的早期表达模式的调节。
3. Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles [J] . Zhang Yina, Lin Shuo, Karakatsani Andromachi, The European Journal of Neuroscience . 2015,第1a2期

机译：小鼠肌肉纺锤体的极地和赤道区域AChR聚集的差异调节。
4. Research on the Interactive Development of Industrial Clusters and Small (Cities) Towns with Characteristics in Western Regions: Taking the Development of Traditional Chinese Medicine Industrial Clusters in Xianyang City of Shaanxi Province as an Example [C] . Xiaoyuan Zhou, Dan Zhao, Yuan Lv International Conference on Culture, Education and Economic Development of Modern Society . 2019

机译：西部地区特征产业集群与小（城市）城镇的互动发展研究 - 以陕西咸阳市中医药产业集群为例
5. The identification of MIG-5/Dishevelled as a CACN-1 interacting protein in Caenorhabditis elegans, using in vivo and in vitro approaches . [D] . Ibourk, Mouna. 2010

机译：使用体内和体外方法鉴定秀丽隐杆线虫中的MIG-5 /杂化为CACN-1相互作用蛋白。
6. MuSK Myasthenia Gravis IgG4 Disrupts the Interaction of LRP4 with MuSK but Both IgG4 and IgG1-3 Can Disperse Preformed Agrin-Independent AChR Clusters [O] . Inga Koneczny, Judith Cossins, Patrick Waters, -1

机译：MuSK重症肌无力IgG4破坏了LRP4与MuSK的相互作用但IgG4和IgG1-3均可分散预先形成的不依赖Agrin的AChR簇
7. Regulation of AChR Clustering by Dishevelled Interacting with MuSK and PAK1 [O] . Luo Zhen G, Wang Qiang, Zhou Jian Z, 2002

机译：通过与MuSK和PAK1相互作用实现AChR簇的调控。

Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.

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