Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart failure and arrhythmogenesis.
Contractile dysfunction and ventricular arrhythmias associated with heart failure have been attributed to aberrant sarcoplasmic reticulum (SR) Ca(2+) cycling. The study of junctin (JCN) and histidine-rich Ca(2+) binding protein (HRC) becomes of particular importance since these proteins have been shown to be critical regulators of Ca(2+) cycling. Specifically, JCN is a SR membrane protein, which is part of the SR Ca(2+) release quaternary structure that also includes the ryanodine receptor, triadin and calsequestrin. Functionally, JCN serves as a bridge between calsequestrin and the Ca(2+) release channel, ryanodine receptor. HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release. Indeed, evidence from genetic models of JCN and HRC indicate that they are important in cardiophysiology as alterations in these proteins affect SR Ca(2+) handling and cardiac function. In addition, downregulation of JCN and HRC may contribute to Ca(2+) cycling perturbations manifest in the failing heart, where their protein levels are significantly reduced. This review examines the roles of JCN and HRC in SR Ca(2+) cycling and their potential significance in heart failure.
Pritchard
Tracy J
TJ
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575, USA.
Kranias
Evangelia G
EG
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008955:Models, Cardiovascular; D009124:Muscle Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D002135:Calcium-Binding Proteins; C489418:Hrc protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins; C068969:HRC protein, human; C498841:Asph protein, mouse; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human