Nonstructural Roles of Junctophilin-2 in the Heart.

IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Daniel F Hutchison, Satadru K Lahiri, Kurt W Prins, Xander H T Wehrens
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引用次数: 0

Abstract

Junctophilin-2 (JPH2) is an essential structural protein that maintains the integrity of junctional membrane complexes (JMCs) in cardiomyocytes, thereby playing its canonical role in excitation-contraction (E-C) coupling. Recent studies reveal novel, nonstructural functions of JPH2 in cardiomyocytes, including regulation of mitochondrial function, lipid metabolism, nuclear signaling, and innate immune responses. Calpain-mediated cleavage of JPH2 generates nuclear fragments, which differentially modulate stress responses. Moreover, full-length JPH2 also localizes to the nucleus, where it forms phase-separated nuclear droplets during oxidative stress. Collectively, these findings highlight JPH2 as a multifunctional protein with critical roles beyond its canonical structural function in E-C coupling.

结膜亲蛋白-2在心脏中的非结构作用。
结膜亲蛋白-2 (Junctophilin-2, JPH2)是维持心肌细胞连接膜复合物(jmc)完整性的重要结构蛋白,在兴奋-收缩(E-C)偶联中发挥着典型的作用。最近的研究揭示了JPH2在心肌细胞中的新的非结构性功能,包括线粒体功能、脂质代谢、核信号传导和先天免疫反应的调节。calpain介导的JPH2裂解产生核片段,其差异调节应激反应。此外,全长JPH2也定位于细胞核,在氧化应激过程中形成相分离的核滴。总的来说,这些发现突出了JPH2作为一种多功能蛋白,在E-C偶联中具有典型的结构功能之外的关键作用。
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来源期刊
JACC: Basic to Translational Science
JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
14.20
自引率
1.00%
发文量
161
审稿时长
16 weeks
期刊介绍: JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.
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