Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain

Abstract

Cardiac muscle contraction requires sarcoplasmic reticulum (SR) Ca2+ release mediated by the quaternary complex comprising the ryanodine receptor (RyR2), calsequestrin (CSQ2), junctin 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 novel perspective for understanding the SR luminal Ca2+ sensor and its involvement in cardiac physiology and disease.