ArticleJCI insight2019
Junctophilin-2 expression rescues atrial dysfunction through polyadic junctional membrane complex biogenesis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- One gene, two modes of inheritance, four diseases: A systematic review of the cardiac manifestation of pathogenic variants in JPH2-encoded junctophilin-2.Trends in cardiovascular medicine · 2023Pooled it
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Dysferlin stabilizes membrane nanodomains of cardiomyocytes after myocardial infarction.Scientific reports · 2026Article
- Versatile Microfluidics Platform for Enhanced Multitarget Super-Resolution Microscopy.ACS nano · 2026Article
- Nanoscale architecture and dynamics of CaJournal of molecular and cellular cardiology plus · 2025Article
- Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction.Circulation · 2025Article
- Mechanisms underlying local CaThe Journal of physiology · 2025Article
- Structure, Function, and Regulation of the Junctophilin Family.Annual review of physiology · 2024Review
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Article
- IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart.Nature communications · 2023Article
- The role of junctophilin proteins in cellular function.Physiological reviews · 2022Review
- Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NTScientific reports · 2022Article
- Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium.American journal of physiology. Heart and circulatory physiology · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cytoskeletal Protein Variants Driving Atrial Fibrillation: Potential Mechanisms of Action.Cells · 2022Review
- Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart.NPJ aging and mechanisms of disease · 2021Article
- Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review.Frontiers in physiology · 2021Review
- Targeting JP2: A New Treatment for Pulmonary Hypertension.Oxidative medicine and cellular longevity · 2021Review
- The RyR2-R2474S Mutation Sensitizes Cardiomyocytes and Hearts to Catecholaminergic Stress-Induced Oxidation of the Mitochondrial Glutathione Pool.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Atrial dysfunction is highly prevalent and associated with increased severity of heart failure. While rapid excitation-contraction coupling depends on axial junctions in atrial myocytes, the molecular basis of atrial loss of function remains unclear. We identified approximately 5-fold lower junctophilin-2 levels in atrial compared with ventricular tissue in mouse and human hearts. In atrial myocytes, this resulted in subcellular expression of large junctophilin-2 clusters at axial junctions, together with highly phosphorylated ryanodine receptor (RyR2) channels. To investigate the contribution of junctophilin-2 to atrial pathology in adult hearts, we developed a cardiomyocyte-selective junctophilin-2-knockdown model with 0 mortality. Junctophilin-2 knockdown in mice disrupted atrial RyR2 clustering and contractility without hypertrophy or interstitial fibrosis. In contrast, aortic pressure overload resulted in left atrial hypertrophy with decreased junctophilin-2 and RyR2 expression, disrupted axial junctions, and atrial fibrosis. Whereas pressure overload accrued atrial dysfunction and heart failure with 40% mortality, additional junctophilin-2 knockdown greatly exacerbated atrial dysfunction with 100% mortality. Strikingly, transgenic junctophilin-2 overexpression restored atrial contractility and survival through de novo biogenesis of polyadic junctional membrane complexes maintained after pressure overload. Our data show a central role of junctophilin-2 cluster disruption in atrial hypertrophy and identify transgenic augmentation of junctophilin-2 as a disease-mitigating rationale to improve atrial dysfunction and prevent heart failure deterioration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.