CASQ1

CASQ1, or calsequestrin-1, is a calcium-binding protein located in the lumen of the sarcoplasmic reticulum (SR) of skeletal muscle. It is encoded by the CASQ1 gene and represents the skeletal muscle isoform of calsequestrin, a family of acidic, high-capacity calcium buffers in the SR.

Function and role in muscle physiology: CASQ1 serves as a low-affinity, high-capacity calcium reservoir that helps store Ca2+ within the SR. By buffering luminal Ca2+ and forming Ca2+-dependent polymers, CASQ1 contributes to the regulation of calcium release during excitation-contraction coupling. It interacts with other components of the SR calcium-release complex, including the ryanodine receptor type 1 (RYR1), triadin, and junctin, to modulate channel activity and maintain Ca2+ homeostasis in skeletal muscle.

Expression and family: CASQ1 is highly expressed in skeletal muscle and is the counterpart to CASQ2, which is the cardiac isoform expressed in heart muscle. Both proteins belong to the calsequestrin family, which coordinates Ca2+ storage and release within the SR across tissues.

Clinical significance: Rare mutations in CASQ1 have been described in inherited skeletal myopathies, sometimes featuring cores or cores-like lesions in muscle fibers and exercise-induced weakness. Experimental models with CASQ1 disruption demonstrate impaired SR Ca2+ handling and reduced muscle performance, underscoring CASQ1’s importance in efficient excitation-contraction coupling.

Structure and localization: CASQ1 is an acidic, Ca2+-binding protein localized to the junctional SR in skeletal muscle, where it helps organize and stabilize the calcium-release machinery necessary for rapid and controlled Ca2+ signaling during muscle contraction.