Ca2+ signaling in striated muscle: the elusive roles of triadin, junctin, and calsequestrin

This review focuses on molecular interactions between calsequestrin, triadin, junctin and the ryanodine receptor in the lumen of the sarcoplasmic reticulum. These interactions modulate changes in Ca2+ release in response to changes in the Ca2+ load within the sarcoplasmic reticulum store in striated muscle and are of fundamental importance to Ca2+ homeostasis, since massive adaptive changes occur when expression of the proteins is manipulated, while mutations in calsequestrin lead to functional changes which can be fatal. We find that calsequestrin plays a different role in the heart and skeletal muscle, enhancing Ca2+ release in the heart, but depressing Ca2+ release in skeletal muscle. We also find that triadin and junctin exert independent influences on the ryanodine receptor in skeletal muscle where triadin alone modifies excitation-contraction coupling, while junctin alone supports functional interactions between calsequestrin and the ryanodine receptor.