Coupling of USP10 de-ubiquitination and chaperone-mediated autophagy causes cardiac sodium channel degradation and cardiac arrhythmias
We identified a novel CMA-mediated pathway regulating degradation of Nav1.5 by coupling with USP10-mediated de-ubiquitination at K430 of Nav1.5, which resulted in reduced INa densities and cardiac conduction defects. Knockdown of USP10 alleviated arrhythmias in Scn5a+/- mice, providing a novel therapeutic strategy for treating arrhythmias with reduced INa.
Authors
- Yimei Du (ORCID: https://orcid.org/0000-0003-1125-0294)
- Tong Zhang (ORCID: https://orcid.org/0000-0003-2377-6779)
- Hongbo Xiong
- Zhibing Lu (ORCID: https://orcid.org/0000-0002-7950-3465)
- Qiongxin Wang (ORCID: https://orcid.org/0000-0003-3697-8708)
- Huanhuan Cai (ORCID: https://orcid.org/0000-0003-3426-8630)
- Di Fan (ORCID: https://orcid.org/0000-0002-7223-0345)
- Zhijie Wang (ORCID: https://orcid.org/0000-0003-4619-0543)
- Qing Kenneth Wang (ORCID: https://orcid.org/0000-0002-2235-6572)
- Zhen Zhou (ORCID: https://orcid.org/0000-0002-7254-2701)
- Di Guo
- Xiangzhan Kong (ORCID: https://orcid.org/0009-0008-9694-3877)
- Lilin Xiang
Institutions
- Wuhan University (CN)
- Hubei Provincial Center for Disease Control and Prevention (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Hubei Provincial Women and Children's Hospital (CN)
- Wuhan Union Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1093/cvr/cvaf214
- Citations
- 1
- Primary Topic
- Heat shock proteins research
- Type
- article
- Field-Weighted Citation Impact
- 0.81