Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells
作者单位：Shanghai Jiaotong University School of Medicine Department of Neurology Tongren Hospital Shanghai Jiaotong University School of Medicine
会议名称：《第十届全国免疫学学术大会》
会议日期：2015年
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
关 键 词：Endoplasmic reticulum stress acetylcholine receptor endocytosis protein degradation skeletal muscle cells myasthenia gravis
摘 要：INTRODUCTION AND OBJECTIVES 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 *** turnover and renewal of acetylcholine receptors contributes to the pathogenesis of myasthenia *** study would like to unveil if and how endoplasmic reticulum(ER)stress is involved in regulating turnover of acetylcholine *** Utilizing ER inducers such as tunicamycin and thapsigargin,we monitored the endocytosis and degradation of acetylcholine receptor in C2C12 myocytes by flow cytometry,confocal microscopy and western blotting,and further tracked the degradation pathway of acetylcholine receptors with diverse *** knockdown of ER stress proteins such as XBP-1 was also applied to confirm the function of ER stress in regulating acetylcholine receptor endocytosis and *** In the present study,we demonstrated that endoplasmic reticulum(ER)stress contributes to acetylcholine receptor degradation in C2C12 *** stress promotes acetylcholine receptor endocytosis and lysosomal degradation,which was dampened by blocking endocytosis or treating with lysosome *** down of ER stress protein XBP-1 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 *** Our studies identify ER stress as a factor promoting acetylcholine receptor degradation through accelerating endocytosis in muscle *** ER stress and/or endocytosis might provide a novel therapeutic approach for myasthenia gravis.