title: alpha-E-catenin inactivation disrupts the cardiomyocyte adherens junction, resulting in cardiomyopathy and susceptibility to wall rupture.
abstract: BACKGROUND
  alpha-E-catenin is a cell adhesion protein, located within the adherens junction, thought to be essential in directly linking the cadherin-based adhesion complex to the actin cytoskeleton. Although alpha-E-catenin is expressed in the adherens junction of the cardiomyocyte intercalated disc, and perturbations in its expression are observed in models of dilated cardiomyopathy, its role in the myocardium remains unknown.
  
  
  RESULTS
  To determine the effects of alpha-E-catenin on cardiomyocyte ultrastructure and disease, we generated cardiac-specific alpha-E-catenin conditional knockout mice (alpha-E-cat cKO). alpha-E-cat cKO mice displayed progressive dilated cardiomyopathy and unique defects in the right ventricle. The effects on cardiac morphology/function in alpha-E-cat cKO mice were preceded by ultrastructural defects in the intercalated disc and complete loss of vinculin at the intercalated disc. alpha-E-cat cKO mice also revealed a striking susceptibility of the ventricular free wall to rupture after myocardial infarction.
  
  
  CONCLUSIONS
  These results demonstrate a clear functional role for alpha-E-catenin in the cadherin/catenin/vinculin complex in the myocardium in vivo. Ablation of alpha-E-catenin within this complex leads to defects in cardiomyocyte structural integrity that result in unique forms of cardiomyopathy and predisposed susceptibility to death after myocardial stress. These studies further highlight the importance of studying the role of alpha-E-catenin in human cardiac injury and cardiomyopathy in the future.
authors.affiliation: Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0613, USA.
authors.forename: Farah
authors.initials: F
authors.lastname: Sheikh
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Chen
authors.forename: Xingqun
authors.initials: X
authors.lastname: Liang
authors.forename: Alain
authors.initials: A
authors.lastname: Hirschy
authors.forename: Antine E
authors.initials: AE
authors.lastname: Stenbit
authors.forename: Yusu
authors.initials: Y
authors.lastname: Gu
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yajima
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Lu
authors.forename: Kirk U
authors.initials: KU
authors.lastname: Knowlton
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Perriard
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D004195:Disease Models, Animal; D004562:Electrocardiography; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000473:pathology / Q000502:physiology*; D009203:Myocardial Infarction / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D018497:Ventricular Dysfunction, Right / Q000235:genetics*; D051178:alpha Catenin / Q000172:deficiency / Q000235:genetics*
chemical_list: D011506:Proteins; D051178:alpha Catenin