Emerging roles of junctophilin-2 in the heart and implications for cardiac diseases

Abstract

Cardiomyocytes rely on a highly specialized subcellular architecture to maintain normal cardiac function. In a little over a decade, junctophilin-2 (JPH2) has become recognized as a cardiac structural protein critical in forming junctional membrane complexes (JMCs), which are subcellular domains essential for excitation-contraction couplingwithin the heart.While initial studies described the structure of JPH2and its role in anchoring junctional sarcoplasmic reticulum and transverse-tubule (T-tubule) membrane invaginations, recent research has an expanded role of JPH2 in JMC structure and function. Forexample, JPH2is necessary for the development of postnatalT-tubule inmammals. It is also critical for themaintenanceof the complex JMCarchitecture and stabilizationof local ionchannels inmature cardiomyocytes. Loss of this functionbymutations ordown-regulation of protein expression has been linked to hypertrophic cardiomyopathy, arrhythmias, and progression of disease in failing hearts. In this review, we summarize current views on the roles of JPH2 within the heart and how JPH2 dysregulation may contribute to a variety of cardiac diseases. All rights reserved. © The Author 2014.