内吞作用
乙酰胆碱受体
乙酰胆碱
内质网
细胞生物学
神经肌肉接头
受体介导的内吞作用
毒蕈碱乙酰胆碱受体M3
毒蕈碱乙酰胆碱受体M5
心肌细胞
化学
受体
生物
内分泌学
生物化学
神经科学
作者
Ailian Du,Shiqian Huang,Xiaonan Zhao,Yun Zhang,Linggang Zhu,Jingzhong Ding,Congfeng Xu
标识
DOI:10.1016/j.jneuroim.2015.11.024
摘要
After binding by acetylcholine released from a motor neuron, a nicotinic acetylcholine receptor at the neuromuscular junction produces a localized end-plate potential, which leads to muscle contraction. Improper turnover and renewal of acetylcholine receptors contributes to the pathogenesis of myasthenia gravis. In the present study, we demonstrate that endoplasmic reticulum (ER) stress contributes to acetylcholine receptor degradation in C2C12 myocytes. We further show that ER stress promotes acetylcholine receptor endocytosis and lysosomal degradation, which was dampened by blocking endocytosis or treating with lysosome inhibitor. Knockdown of ER stress proteins inhibited acetylcholine receptor endocytosis and degradation, while rescue assay restored its endocytosis and degradation, confirming the effects of ER stress on promoting endocytosis-mediated degradation of junction acetylcholine receptors. Thus, our studies identify ER stress as a factor promoting acetylcholine receptor degradation through accelerating endocytosis in muscle cells. Blocking ER stress and/or endocytosis might provide a novel therapeutic approach for myasthenia gravis.
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