Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 Mutations Disrupt desmosome assembly and stability

Chad Hall, Shumin Li, Hong Li, Valeta Creason, James K. Wahl

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by life-threatening ventricular arrhythmias and fibrofatty replacement of the cardiac tissue. Desmosomes are prominent cell-cell junctions found in a variety of tissues that resist mechanical stress, including the heart, and recruit the intermediate filament cytoskeleton to sites of cell-cell contact. Mutations in several desmosomal components including plakophilin-2 have been identified in ARVC patients; however, the molecular interactions disrupted by plakophilin-2 mutations are currently unknown. To understand the pathological basis of ARVC, the authors analyzed desmosome assembly and stability in epithelial cell lines expressing mutants of plakophilin-2 found in ARVC patients. Mutant plakophilin-2 proteins were unable to disrupt established desmosomes when expressed in an E-cadherinexpressing epithelial cell model; however, they were unable to initiate de novo assembly of desmosomes in an N-cadherinexpressing epithelial cell model. These studies expand our understanding of desmosome assembly and dynamics.

Original languageEnglish (US)
Pages (from-to)15-27
Number of pages13
JournalCell Communication and Adhesion
Volume16
Issue number1-3
DOIs
StatePublished - 2009

Keywords

  • ARVC
  • Desmosome
  • Plakophilin-2

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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