Key result
Co-expression of RyR2 and CSQ2 in a human cell line altered Ca2+-release dynamics compared to cells expressing RyR2 only, demonstrating a direct interaction at the first luminal loop of RyR2.
Demonstrates a direct interaction between RyR2 and CSQ2 that alters calcium release dynamics, providing new insights into the SR luminal calcium sensor.
Does not yet alter clinical practice; leaves open the RyR2 luminal loop as a target pending in vivo validation.
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.
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Handhle et al. (2016) studied this question. Co-expression of RyR2 and CSQ2 vs. Cells expressing RyR2 only was evaluated on Ca2+-release dynamics. Co-expression of RyR2 and CSQ2 in a human cell line altered Ca2+-release dynamics compared to cells expressing RyR2 only, demonstrating a direct interaction at the first luminal loop of RyR2.
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