Plakophilin 2 is required for normal cardiac development

Plakophilin 2 (PKP2), a member of the armadillo protein family, has been shown to be an essential component of heart morphogenesis. Walter Birchmeier and colleagues showed defective cell-cell adhesions in PKP2 knock-out mice, resulting in lethal cardiac damage during gestation. Heart alterations included reduced trabeculation, cardiac wall rupture, disarrayed cytoskeleton, and blood leakage into the pericardiac cavity. The scientists conclude that PKP2 is necessary to both fix the cytoskeletal linker protein, desmoplakin, to the junctional plaques of cardiomyocytes and to function as a stabilizing binding partner of desmosomal cadherins (Journal of Cell Biology, 167 (1) October 11, 2004, pp.149-160).

Following the lead from the Birchmeier lab, Ludwig Thierfelder and colleagues were able to confirm the critical role of PKP2 in desmosome formation and function in individuals affected with arrhythmogenic right ventricular cardiomyopathy (ARVC). (Nature Genetics 36 (11) November 2004, pp. 1162-1164) ARVC results from the replacement of cardiac myocytes with fibrofatty tissue and is clinically characterized by palpitations and ventricular tachyarrhythmias which, in severe forms, often results in sudden cardiac death. In 120 ARVC patients studied, 32 patients (>25%) were shown to carry a mutation in the PKP2 gene. The researchers also found that pedigrees with clinical ARVC and confirmed PKP2 mutations display incomplete penetrance, possibly due to gender, genetic, or epigenetic factors. In addition, the exact mechanism of how the PKP2 mutation affects heart function in humans remains unknown. Further studies are needed to investigate the role of PKP2 in establishing proper cell-cell contacts of cardiomyocytes.

Contact:

Pamela Cohen
p.cohen@mdc-berlin.de
+49 30 9406 2121