Identification of small-molecule ion channel modulators in C. elegans channelopathy models
文献类型：期刊论文
| 作者 | Jiang, Qiang1,2,3; Li, Kai1,2,3; Chen, Xin1,2,3; Liu, Xi-Juan1,2; Yuan, Jie1,2,3; Cai, Shi-Qing1,2; Li, Shuang3; Lu, Wen-Jing4; Lan, Feng4; Li, Shuang5 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2018 |
| 卷号 | 9期号:-页码:3941 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-018-06514-5 |
| 文献子类 | Article |
| 英文摘要 | Ion channels are important therapeutic targets, but the discovery of ion channel drugs remains challenging due to a lack of assays that allow high-throughput screening in the physiological context. Here we report C. elegans phenotype-based methods for screening ion channel drugs. Expression of modified human ether-a-go-go-related gene (hERG) potassium channels in C. elegans results in egg-laying and locomotive defects, which offer indicators for screening small-molecule channel modulators. Screening in worms expressing hERG(A561V), which carries a trafficking-defective mutation A561V known to associate with long-QT syndrome, identifies two functional correctors Prostratin and ingenol-3,20-dibenzoate. These compounds activate PKC epsilon signaling and consequently phosphorylate S606 at the pore region of the channel to promote hERGA561V trafficking to the plasma membrane. Importantly, the compounds correct electrophysiological abnormalities in hiPSC-derived cardiomyocytes bearing a heterozygous CRISPR/Cas9-edited hERG(A561V). Thus, we have developed an in vivo high-throughput method for screening compounds that have therapeutic potential in treating channelopathies. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | LONG QT SYNDROME ; HERG POTASSIUM CHANNEL ; CAENORHABDITIS-ELEGANS ; CARDIAC-ARRHYTHMIA ; AUXILIARY SUBUNITS ; DRUG DISCOVERY ; TRAFFICKING ; MUTATIONS ; PROTEIN ; GENES |
| 语种 | 英语 |
| WOS记录号 | WOS:000445607500012 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/752]  |
| 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.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Neurosci, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci, Shanghai 200031, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Capital Med Univ, Beijing Anzhen Hosp, Beijing Lab Cardiovasc Precis Med, Beijing 100029, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai 200031, Peoples R China; 6.Hosp Sick Children, Dev & Stem Cell Program, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada, |
| 推荐引用方式 GB/T 7714 | Jiang, Qiang,Li, Kai,Chen, Xin,et al. Identification of small-molecule ion channel modulators in C. elegans channelopathy models[J]. NATURE COMMUNICATIONS,2018,9(-):3941. |
| APA | Jiang, Qiang.,Li, Kai.,Chen, Xin.,Liu, Xi-Juan.,Yuan, Jie.,...&,.(2018).Identification of small-molecule ion channel modulators in C. elegans channelopathy models.NATURE COMMUNICATIONS,9(-),3941. |
| MLA | Jiang, Qiang,et al."Identification of small-molecule ion channel modulators in C. elegans channelopathy models".NATURE COMMUNICATIONS 9.-(2018):3941. |
入库方式： OAI收割
来源：上海营养与健康研究所
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