ArticleBasic research in cardiology2020
Nuclear localization of a novel calpain-2 mediated junctophilin-2 C-terminal cleavage peptide promotes cardiomyocyte remodeling.
Article in Basic research in cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- Calpain Mediated Proteolysis of Junctophilin-1 Produces an Aggregation Prone C-Terminal Fragment in Skeletal Muscle.Research square · 2026Article
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- Phosphorylation of RYR1 at SerScience signaling · 2025Article
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- CaInflammation and regeneration · 2025Review
- Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.American journal of physiology. Heart and circulatory physiology · 2024Article
- Artificial intelligence approaches to the volumetric quantification of glycogen granules in EM images of human tissue.The Journal of general physiology · 2024Article
- Targeting calpain-2-mediated junctophilin-2 cleavage delays heart failure progression following myocardial infarction.Journal of molecular and cellular cardiology · 2024Article
- Membrane Curvature Promotes ER-PM Contact Formation via Junctophilin-EHD Interactions.bioRxiv : the preprint server for biology · 2024Article
- Altered myocardial lipid regulation in junctophilin-2-associated familial cardiomyopathies.Life science alliance · 2024Article
- Structure, Function, and Regulation of the Junctophilin Family.Annual review of physiology · 2024Review
- Huntington disease-like 2: insight into neurodegeneration from an African disease.Nature reviews. Neurology · 2024Review
- The roles of intracellular proteolysis in cardiac ischemia-reperfusion injury.Basic research in cardiology · 2023Review
- Speg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads.Communications biology · 2023Article
- Loss of IP3R-BKInternational journal of molecular sciences · 2023Article
- Article
- Sustained over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice through aberrant autophagy.Acta pharmacologica Sinica · 2022Article
- Calcium-Sensing Receptor (CaSR)-Mediated Intracellular Communication in Cardiovascular Diseases.Cells · 2022Review
- The role of junctophilin proteins in cellular function.Physiological reviews · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Patients with HF exhibit a loss of junctophilin-2 (JPH2), a structural protein critical in forming junctional membrane complexes in which excitation-contraction takes place. Several mechanisms have been proposed to mediate the loss of JPH2, one being cleavage by the calcium-dependent protease calpain. The downstream mechanisms underlying HF progression after JPH2 cleavage are presently poorly understood. In this study, we used Labcas to bioinformatically predict putative calpain cleavage sites on JPH2. We identified a cleavage site that produces a novel C-terminal JPH2 peptide (JPH2-CTP) using several domain-specific antibodies. Western blotting revealed elevated JPH2-CTP levels in hearts of patients and mice with HF, corresponding to increased levels of calpain-2. Moreover, immunocytochemistry demonstrated nuclear localization of JPH2-CTP within ventricular myocytes isolated from a murine model of pressure overload-induced HF as well as rat ventricular myocytes treated with isoproterenol. Nuclear localization of JPH2-CTP and cellular remodeling were abrogated by a genetic mutation of the nuclear localization sequence within JPH2-CTP. Taken together, our studies identified a novel C-terminal fragment of JPH2 (JPH2-CTP) generated by calpain-2 mediated cleavage which localizes within the cardiomyocyte nucleus during HF. Blocking nuclear localization of JPH2-CTP protects cardiomyocytes from isoproterenol-induced hypertrophy in vitro. Future in vivo studies of the nuclear role of JPH2-CTP may reveal a causal association with adverse remodeling during HF and establish CTP as a therapeutic target.
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