ArticleCirculation2014
Microtubule-mediated defects in junctophilin-2 trafficking contribute to myocyte transverse-tubule remodeling and Ca2+ handling dysfunction in heart failure.
Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 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.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- A meta-analysis evaluating efficacy and safety of colchicine for prevention of major cardiovascular events in patients with coronary artery disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2023Pooled it
- Vasohibin 1 acts as a key regulator of arrhythmogenesis in pressure-overload-induced cardiac hypertrophy.Acta pharmacologica Sinica · 2026Article
- T-tubular remodeling occurs in a cardiomyocyte-autonomous manner following pathological mechanical stiffness exposure.Journal of molecular and cellular cardiology plus · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling.Nature cardiovascular research · 2026Article
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.RNA biology · 2025Article
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction.Circulation · 2025Article
- CaInflammation and regeneration · 2025Review
- Impact of Sorbs2 dysfunction on cardiovascular diseases.Biochimica et biophysica acta. Molecular basis of disease · 2025Review
- Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis.APL bioengineering · 2025Review
- Probing the CabioRxiv : the preprint server for biology · 2025Article
- Functional analysis of JPH2-knockout cardiomyocytes identifies ECCD as a novel indicator in a human cardiac modelJPH2.Stem cell research & therapy · 2025Article
- The Role of theGenes · 2025Article
- Human induced pluripotent stem cell-derived cardiomyocytes for disease modeling and drug discovery.Frontiers in bioengineering and biotechnology · 2025Review
- From function to structure: how myofibrillogenesis influences the transverse-axial tubular system development and its peculiarities.Frontiers in physiology · 2025Review
- Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.iScience · 2024Article
- Targeting calpain-2-mediated junctophilin-2 cleavage delays heart failure progression following myocardial infarction.Journal of molecular and cellular cardiology · 2024Article
- Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.Circulation · 2024Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCardiac dysfunction in failing hearts of human patients and animal models is associated with both microtubule densification and transverse-tubule (T-tubule) remodeling. Our objective was to investigate whether microtubule densification contributes to T-tubule remodeling and excitation-contraction coupling dysfunction in heart disease. METHODS AND
resultsIn a mouse model of pressure overload-induced cardiomyopathy by transaortic banding, colchicine, a microtubule depolymerizer, significantly ameliorated T-tubule remodeling and cardiac dysfunction. In cultured cardiomyocytes, microtubule depolymerization with nocodazole or colchicine profoundly attenuated T-tubule impairment, whereas microtubule polymerization/stabilization with taxol accelerated T-tubule remodeling. In situ immunofluorescence of heart tissue sections demonstrated significant disorganization of junctophilin-2 (JP2), a protein that bridges the T-tubule and sarcoplasmic reticulum membranes, in transaortic banded hearts as well as in human failing hearts, whereas colchicine injection significantly preserved the distribution of JP2 in transaortic banded hearts. In isolated mouse cardiomyocytes, prolonged culture or treatment with taxol resulted in pronounced redistribution of JP2 from T-tubules to the peripheral plasma membrane, without changing total JP2 expression. Nocodazole treatment antagonized JP2 redistribution. Moreover, overexpression of a dominant-negative mutant of kinesin 1, a microtubule motor protein responsible for anterograde trafficking of proteins, protected against JP2 redistribution and T-tubule remodeling in culture. Finally, nocodazole treatment improved Ca(2+) handling in cultured myocytes by increasing the amplitude of Ca(2+) transients and reducing the frequency of Ca(2+) sparks.
conclusionOur data identify a mechanistic link between microtubule densification and T-tubule remodeling and reveal microtubule-mediated JP2 redistribution as a novel mechanism for T-tubule disruption, loss of excitation-contraction coupling, and heart failure.
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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.