Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain
نویسندگان
چکیده
Cardiac muscle contraction requires sarcoplasmic reticulum (SR) Ca2+ release mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2), calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin. Here, we demonstrate that a direct interaction exists between RyR2 and CSQ2. Topologically, CSQ2 binding occurs at the first luminal loop of RyR2. Co-expression of RyR2 and CSQ2 in a human cell line devoid of the other quaternary complex proteins results in altered Ca2+-release dynamics compared to cells expressing RyR2 only. These findings provide a new perspective for understanding the SR luminal Ca2+ sensor and its involvement in cardiac physiology and disease.
منابع مشابه
Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum.
Triadin is a major membrane protein that is specifically localized in the junctional sarcoplasmic reticulum of skeletal muscle and is thought to play an important role in muscle excitation-contraction coupling. In order to identify the proteins in the skeletal muscle that interact with triadin, the cytoplasmic and luminal domains of triadin were expressed as glutathione S-transferase fusion pro...
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sarcalumenin: phosphorylation, comparison with the skeletal muscle sarcalumenin and modulation of ryanodine receptor. J Membr Biol 1999;170: 39–49. 29. Cala SE, Jones LR. Phosphorylation of cardiac and skeletal muscle calsequestrin isoforms by casein kinase II. Demonstration of a cluster of unique rapidly phosphorylated sites in cardiac calsequestrin. J Biol Chem 1991;266:391–398. 30. Szegedi C...
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Several key proteins have been localized to junctional sarcoplasmic reticulum which are important for Ca2+ release. These include the ryanodine receptor, triadin, and calsequestrin, which may associate into a stable complex at the junctional membrane. We recently purified and cloned a fourth component of this complex, junctin, which exhibits homology with triadin and is the major 125I-calseques...
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