Key result
PKP2 truncating variants impair cardiac contractility by disrupting cell-cell junctions and sarcomere organization.
Plakophilin-2 truncating variants disrupt cardiomyocyte structure and function by destabilizing cell-cell junctions and sarcomeres, revealing a fundamental pathogenic mechanism for cardiomyopathies.
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PKP2 variant effects on junctions and sarcomeres merit human iPSC and tissue model validation; leaves open clinical translation or therapeutic targeting.
tvs impair cardiac tissue contractility by destabilizing cell-cell junctions and in turn disrupting sarcomere stability and organization. These findings highlight the interplay between cell-cell adhesions and sarcomeres required for stabilizing cardiomyocyte structure and function and suggest fundamental pathogenic mechanisms that may be shared among different types of cardiomyopathies.
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Zhang et al. (2021) studied Arrhythmogenic cardiomyopathy. CRISPR-engineered PKP2 truncating variants vs. Wild-type iPSC-CMs was evaluated on Systolic force and stress generation in multicellular cardiac microtissues. PKP2 truncating variants impaired cardiac tissue contractility in multicellular contexts by destabilizing cell-cell junctions and disrupting sarcomere stability and organization.
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