ArticleThe Journal of clinical investigation2020
Auxiliary trafficking subunit GJA1-20k protects connexin-43 from degradation and limits ventricular arrhythmias.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress.Journal of molecular and cellular cardiology · 2026Article
- Injectable platelet-rich plasma-based hydrogels: a controlled release platform for growth factors and cardiac regeneration post-myocardial infarction.Regenerative biomaterials · 2026Article
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Mitochondrial fission controls astrocyte morphogenesis and organization in the cortex.The Journal of cell biology · 2025Article
- Cardiomyocyte Growth on Cardiac Infusible Extracellular Matrix-Coated and Annealed Biodegradable Polyurethane Fibers.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- Viral Infection and Connexin Dysfunction in the Heart.Current cardiology reports · 2025Review
- AAV9-cBIN1 gene therapy rescues chronic heart failure due to ischemic cardiomyopathy in a canine model.Communications medicine · 2025Article
- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.The Journal of cell biology · 2025Article
- Review
- Review
- The activation of P38MAPK Signaling Pathway Impedes the Delivery of the Cx43 to the Intercalated Discs During Cardiac Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2024Article
- Simulation of gap junction formation reveals critical role of Cys disulfide redox state in connexin hemichannel docking.Cell communication and signaling : CCS · 2024Article
- Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Review
- Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.Molecular biology reports · 2024Review
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes.Biologics : targets & therapy · 2024Article
- Determinants of electrical propagation and propagation block in Arrhythmogenic Cardiomyopathy.Journal of molecular and cellular cardiology · 2024Article
- Biochemical Structure and Function of TRAPP Complexes in the Cardiac System.JACC. Basic to translational science · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Connexin-43 (Cx43) gap junctions provide intercellular coupling, which ensures rapid action potential propagation and synchronized heart contraction. Alterations in Cx43 localization and reductions in gap junction coupling occur in failing hearts, contributing to ventricular arrhythmias and sudden cardiac death. Recent reports have found that an internally translated Cx43 isoform, GJA1-20k, is an auxiliary subunit for the trafficking of Cx43 in heterologous expression systems. Here, we have created a mouse model by using CRISPR technology to mutate a single internal translation initiation site in Cx43 (M213L mutation), which generates full-length Cx43, but not GJA1-20k. We found that GJA1M213L/M213L mice had severely abnormal electrocardiograms despite preserved contractile function, reduced total Cx43, and reduced gap junctions, and they died suddenly at 2 to 4 weeks of age. Heterozygous GJA1M213L/WT mice survived to adulthood with increased ventricular ectopy. Biochemical experiments indicated that cytoplasmic Cx43 had a half-life that was 50% shorter than membrane-associated Cx43. Without GJA1-20k, poorly trafficked Cx43 was degraded. The data support that GJA1-20k, an endogenous entity translated independently of Cx43, is critical for Cx43 gap junction trafficking, maintenance of Cx43 protein, and normal electrical function of the mammalian heart.
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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.