Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis
文献类型：期刊论文
| 作者 | Du, Ailian2; Huang, Shiqian3; Zhao, Xiaonan3; Zhang, Shuangyan3; Zhang, Yanyun3,4,5; Xu, Congfeng3,4,5; Feng, Kuan4,5; Huang, Jiefang4,5; Miao, Xiang4,5; Baggi, Fulvio6 |
| 刊名 | AUTOPHAGY
 |
| 出版日期 | 2017 |
| 卷号 | 13期号:11页码:1981-1994 |
| ISSN号 | 1554-8627 |
| 关键词 | carbonic anhydrase 3 chaperone-assisted selective autophagy CHRN endocytosis myasthenia gravis |
| DOI | 10.1080/15548627.2017.1375633 |
| 文献子类 | Article |
| 英文摘要 | Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN internalization via a lipid raft-mediated pathway, leading to accelerated degradation of postsynaptic CHRN. Activation of CAR3 reduces CHRN degradation by suppressing receptor endocytosis. CAR3 exerts this effect by suppressing chaperone-assisted selective autophagy via interaction with BAG3 (BCL2-associated athanogene 3) and by dampening endoplasmic reticulum stress. Collectively, our study illustrates that skeletal muscle cell CAR3 is critical for CHRN homeostasis in the neuromuscular junction, and its deficiency leads to accelerated degradation of CHRN and development of myasthenia gravis, potentially revealing a novel therapeutic approach for this disorder. |
| 学科主题 | Cell Biology |
| WOS关键词 | NICOTINIC ACETYLCHOLINE-RECEPTORS ; CLATHRIN-INDEPENDENT ENDOCYTOSIS ; UNFOLDED PROTEIN RESPONSE ; REGULATORY T-CELLS ; SKELETAL-MUSCLE ; MEDIATED ENDOCYTOSIS ; MOUSE MODEL ; MECHANISMS ; AUTOPHAGY ; AUTOANTIBODIES |
| 语种 | 英语 |
| 出版者 | TAYLOR & FRANCIS INC |
| WOS记录号 | WOS:000418882900014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1103]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chapman Univ, Sch Pharm, Dept Biomed & Pharmaceut Sci, Irvine, CA USA; 2.Shanghai Jiao Tong Univ, Tongren Hosp, Dept Neurol, Sch Med SJTUSM, Shanghai, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Shanghai Inst Immunol, 225 South Chongqing Rd, Shanghai 200025, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China; 5.SJTUSM, Shanghai, Peoples R China; 6.Fdn Ist Neurol Carlo Besta, Neurol Neuroimmunol & Neuromuscular Dis Unit 4, Milan, Italy; 7.Fudan Univ, Huashan Hosp, Dept Neurol, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China; 8.Fudan Univ, Inst Neurol, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Du, Ailian,Huang, Shiqian,Zhao, Xiaonan,et al. Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis[J]. AUTOPHAGY,2017,13(11):1981-1994. |
| APA | Du, Ailian.,Huang, Shiqian.,Zhao, Xiaonan.,Zhang, Shuangyan.,Zhang, Yanyun.,...&,.(2017).Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis.AUTOPHAGY,13(11),1981-1994. |
| MLA | Du, Ailian,et al."Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis".AUTOPHAGY 13.11(2017):1981-1994. |
入库方式： OAI收割
来源：上海营养与健康研究所
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