ArticleTraffic (Copenhagen, Denmark)2014
A 14-3-3 mode-1 binding motif initiates gap junction internalization during acute cardiac ischemia.
Article in Traffic (Copenhagen, Denmark), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 87 citations in OpenAlex.
- Optoelectronic Biohybrid Platform Enables Light-Controlled Cardiac Structural and Functional Feedback.Cell biomaterials · 2026Article
- 14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses.The Journal of physiology · 2026Review
- Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025Article
- Left Ventricular Unloading With Assist Device Implantation Increases GJA1-20k Expression in Patients With Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Viral Infection and Connexin Dysfunction in the Heart.Current cardiology reports · 2025Review
- Article
- The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.iScience · 2024Article
- Determinants of electrical propagation and propagation block in Arrhythmogenic Cardiomyopathy.Journal of molecular and cellular cardiology · 2024Article
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity.Cell biology and toxicology · 2023Article
- HumanizedCells · 2022Article
- Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.Frontiers in cardiovascular medicine · 2022Review
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
- Connecting different heart diseases through intercellular communication.Biology open · 2021Review
- Coupling between cardiac cells-An important determinant of electrical impulse propagation and arrhythmogenesis.Biophysics reviews · 2021Review
- Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
- Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes.Life science alliance · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Altered phosphorylation and trafficking of connexin 43 (Cx43) during acute ischemia contributes to arrhythmogenic gap junction remodeling, yet the critical sequence and accessory proteins necessary for Cx43 internalization remain unresolved. 14-3-3 proteins can regulate protein trafficking, and a 14-3-3 mode-1 binding motif is activated upon phosphorylation of Ser373 of the Cx43 C-terminus. We hypothesized that Cx43(Ser373) phosphorylation is important to pathological gap junction remodeling. Immunofluorescence in human heart reveals the enrichment of 14-3-3 proteins at intercalated discs, suggesting interaction with gap junctions. Knockdown of 14-3-3τ in cell lines increases gap junction plaque size at cell-cell borders. Cx43(S373A) mutation prevents Cx43/14-3-3 complexing and stabilizes Cx43 at the cell surface, indicating avoidance of degradation. Using Langendorff-perfused mouse hearts, we detect phosphorylation of newly internalized Cx43 at Ser373 and Ser368 within 30 min of no-flow ischemia. Phosphorylation of Cx43 at Ser368 by protein kinase C and Ser255 by mitogen-activated protein kinase has previously been implicated in Cx43 internalization. The Cx43(S373A) mutant is resistant to phosphorylation at both these residues and does not undergo ubiquitination, revealing Ser373 phosphorylation as an upstream gatekeeper of a posttranslational modification cascade necessary for Cx43 internalization. Cx43(Ser373) phosphorylation is a potent target for therapeutic interventions to preserve gap junction coupling in the stressed myocardium.
Indexed as
Identifiers
What OpenQuestion holds
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.