Recent advances in understanding skeletal and cardiac muscle function have evolved through recognition of the role played by the intracellular sarcoplasmic reticulum (SR) calcium store in contraction. The key proteins in this store are the calcium binding protein calsequestrin(CSQ), the ryanodine receptor (RyR) calcium release channel and the anchoring proteins triadin and junctin. Together, these proteins form a luminal calcium sensing complex, capable of sensing/regulating calcium store load and RyR calcium release.
Our long-term focus has been on identifying the role of triadin and junctin in modulating SR calcium release and we identified independent and functionally significant roles for both proteins in regulating skeletal RyR (RyR1) activity. We found that junctin facilitates interactions between CSQ and RyR1 that are important in maintaining and conserving calcium concentrations within the stores. On the other hand, triadin may support EC coupling through long-range interactions with the RyR that allow cross-talk between luminal and cytoplasmic residues.
Our recent foci have been on identifying the critical regions that support both the binding and functional interactions between triadin, junctin and RyR1. We identified a) those residues on triadin that form the RyR1 activation domain, b) the essential residues on RyR1 and triadin which support their physical interaction and c) a novel physical and functional interaction between cytoplasmic domains of RyR1 and junctin. Taken together, our results support the notion that junctin, triadin, CSQ and RyR1 form a tightly interacting machine that in vivo ensures optimal EC coupling and SR calcium release.