Calsequestrin Structure, function, and evolution

Calsequestrin is the major Ca binding protein in the sarcoplasmic reticulum (SR), serves as the main Ca storage and buffering protein and is an important regulator of Ca release channels in both skeletal and cardiac muscle. It is anchored at the junctional SR membrane through interactions with membrane proteins and undergoes reversible polymerization with increasing Ca concentration. Calsequestrin provides high local Ca at the junctional SR and communicates changes in luminal Ca concentration to Ca release channels, thus it is an essential component of excitation-contraction coupling. Recent studies reveal new insights on calsequestrin trafficking, Ca binding, protein evolution, protein-protein interactions, stress responses and the molecular basis of related human muscle disease, including catecholaminergic polymorphic ventricular tachycardia (CPVT). Here we provide a comprehensive overview of calsequestrin, with recent advances in structure, diverse functions, phylogenetic analysis, and its role in muscle physiology, stress responses and human pathology.