Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C. Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V. Jossy, Megan L. Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R. Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu
{"title":"Identification of an ionic mechanism for ERα-mediated rapid excitation in neurons","authors":"Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C. Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V. Jossy, Megan L. Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R. Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu","doi":"10.1126/sciadv.adp0696","DOIUrl":null,"url":null,"abstract":"The major female ovarian hormone, 17β-estradiol (E <jats:sub>2</jats:sub> ), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E <jats:sub>2</jats:sub> , but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E <jats:sub>2</jats:sub> and reduced by its depletion. In addition, Clic1 currents are required to mediate the E <jats:sub>2</jats:sub> -induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E <jats:sub>2</jats:sub> on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E <jats:sub>2</jats:sub> -induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E <jats:sub>2</jats:sub> .","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/sciadv.adp0696","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
The major female ovarian hormone, 17β-estradiol (E 2 ), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E 2 , but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E 2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E 2 -induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E 2 on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E 2 -induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E 2 .
期刊介绍:
Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.