Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: protein mislocalization versus epitope masking

Cardiovasc Res. 2016 Feb 1;109(2):260-71. doi: 10.1093/cvr/cvv270. Epub 2015 Dec 16.

Abstract

Aims: To examine the relevance and cause of reduced plakoglobin IF in intercalated discs for arrhythmogenic right ventricular cardiomyopathy (ARVC) and ARVC-like disease in mouse and human.

Methods and results: Normalized semi-quantitative IF measurements were performed in a standardized format in desmoglein 2-mutant mice with an ARVC-like phenotype (n = 6) and in cardiac biopsies from humans with ARVC and non-ARVC heart disease (n = 10). Reduced plakoglobin staining was detectable in ARVC only with one antibody directed against a defined epitope but not with three other antibodies reacting with different epitopes of plakoglobin.

Conclusions: Reduced plakoglobin staining in intercalated discs of heart tissue from human ARVC patients and in a murine ARVC model is caused by alterations in epitope accessibility and not by protein relocalization.

Keywords: Area composita; Armadillo repeat; Desmosome; Wnt signalling; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Arrhythmogenic Right Ventricular Dysplasia / genetics
  • Arrhythmogenic Right Ventricular Dysplasia / metabolism*
  • Desmoplakins / genetics
  • Desmoplakins / metabolism*
  • Desmosomes / metabolism
  • Disease Models, Animal
  • Epitopes / genetics
  • Female
  • Humans
  • Male
  • Mice, Knockout
  • Middle Aged
  • Myocardium / metabolism*
  • Phenotype
  • Young Adult
  • gamma Catenin / genetics
  • gamma Catenin / metabolism*

Substances

  • Desmoplakins
  • Epitopes
  • JUP protein, human
  • Jup protein, mouse
  • gamma Catenin