Regulatory roles of junctin in sarcoplasmic reticulum calcium cycling and myocardial function.
Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle. Within this complex, calsequestrin, triadin, and JCN appear to be critical for normal regulation of ryanodine receptor-mediated calcium (Ca) release. Junctin and triadin exhibit 60% to 70% amino acid homology in their transmembrane domains, including repeated KEKE motifs important for macromolecular protein-protein interactions within their SR luminal tails. Recent studies have uncovered functional roles of both JCN and triadin in the mouse heart, using transgenic overexpression strategies, which exhibit varying phenotypes including mild SR structural alterations, prolongation of Ca transient decay, impaired relaxation, and cardiac hypertrophy and/or heart failure. More specifically, both in vitro adenoviral gene transfer and in vivo gene-targeting techniques to manipulate JCN expression levels have shown that JCN is an essential factor in maintaining normal cardiac Ca handling and cardiac function. This article reviews the new findings on the regulatory roles of JCN in cardiac SR Ca cycling and contractility, with special emphasis on the effects of JCN ablation on delayed after depolarization-induced arrhythmias and premature mortality in mouse models.
Fan
Guo-Chang
GC
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA.
Yuan
Qunying
Q
Kranias
Evangelia G
EG
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D006899:Mixed Function Oxygenases / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C498841:Asph protein, mouse; D006899:Mixed Function Oxygenases