Authors
Marina Cerrone, Jerome Montnach, Xianming Lin, Yan-Ting Zhao, Mingliang Zhang, Esperanza Agullo-Pascual, Alejandra Leo-Macias, Francisco J Alvarado, Igor Dolgalev, Thomas V Karathanos, Kabir Malkani, Chantal JM Van Opbergen, Joanne JA Van Bavel, Hua-Qian Yang, Carolina Vasquez, David Tester, Steven Fowler, Fengxia Liang, Eli Rothenberg, Adriana Heguy, Gregory E Morley, William A Coetzee, Natalia A Trayanova, Michael J Ackerman, Toon AB Van Veen, Hector H Valdivia, Mario Delmar
Publication date
2017/7/24
Journal
Nature communications
Volume
8
Issue
1
Pages
106
Publisher
Nature Publishing Group UK
Description
Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell–cell adhesion. Mutations in human PKP2 associate with a life-threatening arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mouse to demonstrate that in addition to its role in cell adhesion, PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1.2) and Trdn (coding for triadin), and protein levels of calsequestrin-2 (Casq2). These factors combined lead to disruption of intracellular calcium homeostasis and isoproterenol-induced arrhythmias that are prevented by flecainide treatment. We propose a previously unrecognized …
Scholar articles
Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm
M Cerrone, J Montnach, X Lin, YT Zhao, M Zhang… - Nature communications, 2017