Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells
Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells
复制标题
内质网应激通过促进骨骼肌细胞的内吞作用导致乙酰胆碱受体降解。
DOI：
10.1016/j.jneuroim.2015.11.024
复制
发表时间：
2016-01-15
影响因子：
3.3
通讯作者：
Xu, Congfeng
中科院分区：
文献类型：
--
作者：
Du, Ailian;Huang, Shiqian;Xu, Congfeng
在与运动神经元释放的乙酰胆碱结合后，神经肌肉接头处的烟碱乙酰胆碱受体产生局部终板电位，导致肌肉收缩。乙酰胆碱受体的不适当更新和更新有助于重症肌无力的发病机制。在本研究中，我们证明，内质网（ER）的压力有助于C2 C12肌细胞乙酰胆碱受体的降解。我们进一步表明，内质网应激促进乙酰胆碱受体的内吞和溶酶体降解，这是通过阻断内吞或用溶酶体抑制剂处理抑制。ER应激蛋白的敲低抑制乙酰胆碱受体的内吞和降解，而救援测定恢复其内吞和降解，证实了ER应激促进内吞介导的接头乙酰胆碱受体降解的作用。因此，我们的研究确定内质网应激作为一个因素，促进乙酰胆碱受体降解，通过加速内吞在肌肉细胞。阻断内质网应激和/或内吞作用可能为重症肌无力提供一种新的治疗方法。(C)2015 Elsevier B. V.版权所有。
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. (C) 2015 Elsevier B.V. All rights reserved.