An ll-lumen-ating look at ryanodine receptor modulation by disruption in triadin and calsequestrin interactions in cardiac myocytes

摘要

In cardiac muscle, ryanodine receptors (RyR) govern the release of calcium from the sarcoplasmic reticulum (SR). Among the various proteins that are involved in the functional modulation of single channels, triadin (Trd), junctin (Jn) and calsequestrin (CASQ2) are three that reside in the SR lumen. CASQ2, a high capacity calcium buffer, also has a secondary role as a luminal calcium sensor that inhibits RyR opening at low luminal calcium levels. Interactions of CASQ2 with RyR appear to be mediated through Trd and Jn as these proteins have binding sites for both CASQ2 and RyR. The domain structures of Trd and Jn are very similar: both proteins contain a KEKE protein-protein binding motif that is thought to be involved in interactions of Trd and Jn with each other and with RyR2 and CASQ2. The region identified as the CASQ2 binding region in Trd is a 25 amino acid site (200-224) that contains a single KEKE motif.