Fig. 10
From: Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm
Diagrammatic representation of the function of PKP2 in the adult heart. PKP2 scaffolds a signaling node at the intercalated disc. From that position, it covers four known functions: Maintains intercellular coupling and sodium channel function, modulates transcription, and facilitates cell–cell adhesion. In the present study, we show that transcriptional regulation impacts on [Ca2+]i homeostasis. These functions are necessary for normal electrical and mechanical function. Loss or mutations in PKP2 (signaled by the black horizontal dotted line) could independently impair electrical (blue) or mechanical (red) function. A predominant effect in one of these descending branches would yield either an electrical phenotype (resembling Brugada syndrome—BrS—or resembling catecholaminergic polymorphic ventricular tachycardia—CPVT), a mechanical phenotype (e.g., dilated cardiomyopathy) or a combination of both, which would yield the “classic” phenotype of ARVC
