Identification of an ionic mechanism for ERα-mediated rapid excitation in neurons
The major female ovarian hormone, 17β-estradiol (E<sub>2</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<sub>2</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<sub>2</sub> and reduced by its depletion. In addition, Clic1 currents are required to mediate the E<sub>2</sub>-induced rapid excitations in multiple brain ERα populations. Further, genetic disruption of Clic1 in hypothalamic ERα neurons blunts the regulations of E<sub>2</sub> on female body weight balance. In conclusion, we identified the Clic1 chloride channel as a key mediator for E<sub>2</sub>-induced rapid neuronal excitation, which may have a broad impact on multiple neurobiological processes regulated by E<sub>2</sub>.
Authors
- Yanlin He (ORCID: https://orcid.org/0000-0002-5471-9016)
- Longlong Tu (ORCID: https://orcid.org/0000-0002-6955-6002)
- Na Yin (ORCID: https://orcid.org/0000-0001-6026-2721)
- Yongxiang Li (ORCID: https://orcid.org/0000-0002-0631-5391)
- Olivia Z. Ginnard (ORCID: https://orcid.org/0000-0002-8175-6357)
- Kaifan Yu (ORCID: https://orcid.org/0000-0002-5018-3744)
- Shaodong Guo (ORCID: https://orcid.org/0000-0001-5126-731X)
- Qingzhuo Liu (ORCID: https://orcid.org/0009-0003-1243-2783)
- Jean‐François Arnal (ORCID: https://orcid.org/0000-0003-2229-6300)
- Yong Xu (ORCID: https://orcid.org/0000-0002-4908-1572)
- Yang He (ORCID: https://orcid.org/0000-0002-7460-5649)
- Pierre Gourdy (ORCID: https://orcid.org/0000-0002-5362-3813)
- Benjamin Russell Arenkiel (ORCID: https://orcid.org/0000-0001-9047-2420)
- Françoise Lenfant (ORCID: https://orcid.org/0000-0003-0024-7241)
- Kristie Conde (ORCID: https://orcid.org/0000-0002-9525-4606)
- Yue Deng (ORCID: https://orcid.org/0000-0001-8874-911X)
- Peiyu Gao
- Jonathan C. Bean (ORCID: https://orcid.org/0000-0002-8007-2383)
- Xing Fang (ORCID: https://orcid.org/0000-0001-9349-799X)
- Hesong Liu (ORCID: https://orcid.org/0000-0003-3768-1463)
- Sanika V Jossy (ORCID: https://orcid.org/0009-0007-9619-7985)
- Zhao Wang (ORCID: https://orcid.org/0000-0003-4897-9986)
- Mengjie Wang (ORCID: https://orcid.org/0000-0003-3637-4787)
- Chunmei Wang (ORCID: https://orcid.org/0000-0001-8104-6892)
- Yongjie Yang (ORCID: https://orcid.org/0000-0002-2354-4727)
- Bing Cheng Feng (ORCID: https://orcid.org/0000-0002-7403-8402)
- Junying Han
- Meng Yu (ORCID: https://orcid.org/0000-0002-8007-3378)
- Yuxue Yang
- Hailan Liu (ORCID: https://orcid.org/0000-0003-3724-4351)
- Huey Zhong Wong
- Megan L. Burt
Institutions
- Pennington Biomedical Research Center (US)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Baylor College of Medicine (US)
- Texas College (US)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Children's Nutrition Research Center at Baylor College of Medicine (US)
- Texas A&M University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1126/sciadv.adp0696
- Citations
- 8
- Primary Topic
- Neurobiology and Insect Physiology Research
- Type
- article
- Field-Weighted Citation Impact
- 2.15
Funders
- U.S. Department of Agriculture
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Université de Toulouse
- Agricultural Research Service