Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

作者：Hall Chad; Li Shumin; Li Hong; Creason Valeta; Wahl James K III^*

来源：Cell Communication and Adhesion, 2009, 16(1-3): 15-27.

DOI：10.1080/15419060903009329

• ARVC
• desmosome
• plakophilin-2

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-cadherin-expressing epithelial cell model; however, they were unable to initiate de novo assembly of desmosomes in an N-cadherin-expressing epithelial cell model. These studies expand our understanding of desmosome assembly and dynamics.

• 出版日期2009