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Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia

(2012) JOURNAL OF CELL SCIENCE. 125(4). p.1058-1067
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Abstract
It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in the heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological and molecular data indicate a mixing of adherens junctional and desmosomal components, resulting in a 'hybrid adhering junction' or 'area composita'. The alpha-catenin family member alpha T-catenin, part of the N-cadherin-catenin adhesion complex in the heart, is the only alpha-catenin that interacts with the desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that alpha T-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. To investigate the role of alpha T-catenin in the heart, gene targeting technology was used to delete the Ctnna3 gene, encoding alpha T-catenin, in the mouse. The alpha T-catenin-null mice are viable and fertile; however, the animals exhibit progressive cardiomyopathy. Adherens junctional and desmosomal proteins were unaffected by loss of alpha T-catenin, with the exception of the desmosomal protein PKP2. Immunogold labeling at the ICD demonstrated in the alpha T-catenin-null heart a preferential reduction of PKP2 at the area composita compared with the desmosome. Furthermore, gap junction protein Cx43 was reduced at the ICD, including its colocalization with N-cadherin. Gap junction remodeling in alpha T-catenin-knockout hearts was associated with an increased incidence of ventricular arrhythmias after acute ischemia. This novel animal model demonstrates for the first time how perturbation in alpha T-catenin can affect both PKP2 and Cx43 and thereby highlights the importance of understanding the crosstalk between the junctional proteins of the ICD and its implications for arrhythmogenic cardiomyopathy.
Keywords
Cardiac intercalated disc, Adherens junction, BETA-CATENIN, PLAKOPHILIN-2, AREA-COMPOSITA, INTERCALATED DISC, CELLS, GENE, VERTEBRATES, PROTEIN, CONNEXIN43, RABBIT PAPILLARY-MUSCLE, Desmosome, Plakophilin-2, Gap junction, Connexin43, alpha-catenin

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Please use this url to cite or link to this publication:

Chicago
Li, Jifen, Steven Goossens, Jolanda van Hengel, Erhe Gao, Lan Cheng, Koen Tyberghein, Xiying Shang, Riet De Rycke, Frans Van Roy, and Glenn L Radice. 2012. “Loss of αT-catenin Alters the Hybrid Adhering Junctions in the Heart and Leads to Dilated Cardiomyopathy and Ventricular Arrhythmia Following Acute Ischemia.” Journal of Cell Science 125 (4): 1058–1067.
APA
Li, Jifen, Goossens, S., van Hengel, J., Gao, E., Cheng, L., Tyberghein, K., Shang, X., et al. (2012). Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia. JOURNAL OF CELL SCIENCE, 125(4), 1058–1067.
Vancouver
1.
Li J, Goossens S, van Hengel J, Gao E, Cheng L, Tyberghein K, et al. Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia. JOURNAL OF CELL SCIENCE. 2012;125(4):1058–67.
MLA
Li, Jifen, Steven Goossens, Jolanda van Hengel, et al. “Loss of αT-catenin Alters the Hybrid Adhering Junctions in the Heart and Leads to Dilated Cardiomyopathy and Ventricular Arrhythmia Following Acute Ischemia.” JOURNAL OF CELL SCIENCE 125.4 (2012): 1058–1067. Print.
@article{2100466,
  abstract     = {It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in the heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological and molecular data indicate a mixing of adherens junctional and desmosomal components, resulting in a 'hybrid adhering junction' or 'area composita'. The alpha-catenin family member alpha T-catenin, part of the N-cadherin-catenin adhesion complex in the heart, is the only alpha-catenin that interacts with the desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that alpha T-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. To investigate the role of alpha T-catenin in the heart, gene targeting technology was used to delete the Ctnna3 gene, encoding alpha T-catenin, in the mouse. The alpha T-catenin-null mice are viable and fertile; however, the animals exhibit progressive cardiomyopathy. Adherens junctional and desmosomal proteins were unaffected by loss of alpha T-catenin, with the exception of the desmosomal protein PKP2. Immunogold labeling at the ICD demonstrated in the alpha T-catenin-null heart a preferential reduction of PKP2 at the area composita compared with the desmosome. Furthermore, gap junction protein Cx43 was reduced at the ICD, including its colocalization with N-cadherin. Gap junction remodeling in alpha T-catenin-knockout hearts was associated with an increased incidence of ventricular arrhythmias after acute ischemia. This novel animal model demonstrates for the first time how perturbation in alpha T-catenin can affect both PKP2 and Cx43 and thereby highlights the importance of understanding the crosstalk between the junctional proteins of the ICD and its implications for arrhythmogenic cardiomyopathy.},
  author       = {Li, Jifen and Goossens, Steven and van Hengel, Jolanda and Gao, Erhe and Cheng, Lan and Tyberghein, Koen and Shang, Xiying and De Rycke, Riet and Van Roy, Frans and Radice, Glenn L},
  issn         = {0021-9533},
  journal      = {JOURNAL OF CELL SCIENCE},
  keywords     = {Cardiac intercalated disc,Adherens junction,BETA-CATENIN,PLAKOPHILIN-2,AREA-COMPOSITA,INTERCALATED DISC,CELLS,GENE,VERTEBRATES,PROTEIN,CONNEXIN43,RABBIT PAPILLARY-MUSCLE,Desmosome,Plakophilin-2,Gap junction,Connexin43,alpha-catenin},
  language     = {eng},
  number       = {4},
  pages        = {1058--1067},
  title        = {Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia},
  url          = {http://dx.doi.org/10.1242/jcs.098640},
  volume       = {125},
  year         = {2012},
}

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