ArticleCirculation2011
Disrupted junctional membrane complexes and hyperactive ryanodine receptors after acute junctophilin knockdown in mice.
Article in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
What it found
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Who cites it
180 citing papers in PubMed, 257 citations in OpenAlex.
- Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM with heart failure.PloS one · 2018Trial
- Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- JP2 and JCN Crosstalk Abrogate MURF1-Mediated JCN Ubiquitination and Degradation in Cardiomyocytes.JACC. Basic to translational science · 2026Article
- Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.JACC. Clinical electrophysiology · 2026Article
- Active Colitis Attenuates Ventricular Excitation-Contraction Coupling by T-Tubular Remodeling.Biomolecules · 2026Article
- S165F mutation-induced Junctophilin-2 autoinhibition impairs CaCommunications biology · 2025Article
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction.Circulation · 2025Article
- Role of Dyadic Proteins in Proper Heart Function and Disease.International journal of molecular sciences · 2025Review
- Mechanisms underlying local CaThe Journal of physiology · 2025Article
- CaInflammation and regeneration · 2025Review
- Functional analysis of JPH2-knockout cardiomyocytes identifies ECCD as a novel indicator in a human cardiac modelJPH2.Stem cell research & therapy · 2025Article
- RBFOX2 induces osteogenic differentiation by Jph2 expression in MC3T3-E1 preosteoblast cells.Molecular biology reports · 2025Article
- Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.Circulation · 2025Article
- A New Mechanism of Supraventricular Tachycardia: Gene Mutation.Current cardiology reviews · 2025Review
- Junctophilin-2 is a double-stranded RNA-binding protein that regulates cardiomyocyte-autonomous innate immune response.Biochemical and biophysical research communications · 2024Article
- Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.iScience · 2024Article
- Loss-of-function variants inJournal of medical genetics · 2024Article
- Targeting calpain-2-mediated junctophilin-2 cleavage delays heart failure progression following myocardial infarction.Journal of molecular and cellular cardiology · 2024Article
120 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundExcitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and Ca2+ release channels on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss of junctional membrane complexes and embryonic lethality in germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role in junctional membrane complex formation and the Ca(2+)-induced Ca(2+) release process in the heart. Our recent work demonstrated loss-of-function mutations in JPH2 in patients with hypertrophic cardiomyopathy. METHODS AND
resultsTo elucidate the role of JPH2 in the heart, we developed a novel approach to conditionally reduce JPH2 protein levels using RNA interference. Cardiac-specific JPH2 knockdown resulted in impaired cardiac contractility, which caused heart failure and increased mortality. JPH2 deficiency resulted in loss of excitation-contraction coupling gain, precipitated by a reduction in the number of junctional membrane complexes and increased variability in the plasmalemma-sarcoplasmic reticulum distance.
conclusionsLoss of JPH2 had profound effects on Ca2+ release channel inactivation, suggesting a novel functional role for JPH2 in regulating intracellular Ca2+ release channels in cardiac myocytes. Thus, our novel approach of cardiac-specific short hairpin RNA-mediated knockdown of junctophilin-2 has uncovered a critical role for junctophilin in intracellular Ca2+ release in the heart.
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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.