| First Author | Li J | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 4 | Pages | 1058-67 |
| PubMed ID | 22421363 | Mgi Jnum | J:197814 |
| Mgi Id | MGI:5494560 | Doi | 10.1242/jcs.098640 |
| Citation | Li J, et al. (2012) Loss of alphaT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia. J Cell Sci 125(Pt 4):1058-67 |
| abstractText | 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 alphaT-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 alphaT-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. To investigate the role of alphaT-catenin in the heart, gene targeting technology was used to delete the Ctnna3 gene, encoding alphaT-catenin, in the mouse. The alphaT-catenin-null mice are viable and fertile; however, the animals exhibit progressive cardiomyopathy. Adherens junctional and desmosomal proteins were unaffected by loss of alphaT-catenin, with the exception of the desmosomal protein PKP2. Immunogold labeling at the ICD demonstrated in the alphaT-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 alphaT-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 alphaT-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. |
