ArticleScientific reports2017
Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Single Cell Mechanics in Disease Progression.Small science · 2026Review
- Endurance Training Provokes Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Heterozygous Desmoglein-2 Mutants: Alleviation by Preload Reduction.Biomedicines · 2024Article
- Integrated Microfluidics for Single-Cell Separation and On-Chip Analysis: Novel Applications and Recent Advances.Small science · 2024Article
- Cardiac desmosomal adhesion relies on ideal-, slip- and catch bonds.Scientific reports · 2024Article
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing.Frontiers in cardiovascular medicine · 2023Article
- Reactivation of PPARActa pharmaceutica Sinica. B · 2023Article
- Desmoglein 2 can undergo CaBiophysical journal · 2022Article
- Elastic versus brittle mechanical responses predicted for dimeric cadherin complexes.Biophysical journal · 2022Article
- Genetic predisposition study of heart failure and its association with cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2022Review
- Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design.Journal of cardiovascular development and disease · 2020Review
- Genetic Animal Models for Arrhythmogenic Cardiomyopathy.Frontiers in physiology · 2020Review
- Single-molecule studies of classical and desmosomal cadherin adhesion.Current opinion in biomedical engineering · 2019Article
- KC21 Peptide Inhibits Angiogenesis and Attenuates Hypoxia-Induced Retinopathy.Journal of cardiovascular translational research · 2019Article
- Two pedigrees with arrhythmogenic right ventricular cardiomyopathy linked with R49H and F531C mutation inHuman genome variation · 2019Article
- Exploring the Sulfatase 1 Catch Bond Free Energy Landscape using Jarzynski's Equality.Scientific reports · 2018Article
- Genetics of and pathogenic mechanisms in arrhythmogenic right ventricular cardiomyopathy.Biophysical reviews · 2018Review
- Molecular insights into cardiomyopathies associated with desmin (DES) mutations.Biophysical reviews · 2018Review
- Atomic Force Microscopy Provides New Mechanistic Insights into the Pathogenesis of Pemphigus.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC. Using single molecule force spectroscopy and applying Jarzynski's equality we determined the kinetics and thermodynamics of Dsg2 homophilic binding. Notably, the free energy landscape of Dsg2 dimerization exposes a high activation barrier which is in line with the proposed strand-swapping binding motif. Although the binding motif is not directly affected by the mutations the binding kinetics differ significantly from the wildtype. Furthermore, we applied a dispase based cell dissociation assay using HT1080 cell lines over expressing Dsg2 wildtype and mutants, respectively. Our molecular and cellular results consistently demonstrate that Dsg2 mutations can heavily affect homophilic Dsg2 interactions. Furthermore, the full thermodynamic and kinetic description of Dsg2 dimerization provides a consistent model of the so far discussed homophilic cadherin binding.
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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.