alpha-E-catenin inactivation disrupts the cardiomyocyte adherens junction, resulting in cardiomyopathy and susceptibility to wall rupture.
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.
Sheikh
Farah
F
Department of Medicine, University of California-San Diego, La Jolla, CA 92093-0613, USA.
Chen
Yinhong
Y
Chen
Yinghong
Y
Liang
Xingqun
X
Hirschy
Alain
A
Stenbit
Antine E
AE
Gu
Yusu
Y
Dalton
Nancy D
ND
Yajima
Toshitaka
T
Lu
Yingchun
Y
Knowlton
Kirk U
KU
Peterson
Kirk L
KL
Perriard
Jean-Claude
JC
Chen
Ju
J
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*
D011506:Proteins; D051178:alpha Catenin