Calsequestrin-2 (CASQ2) is a calcium-binding protein predominantly found in cardiac muscle and slow-twitch skeletal muscle. It plays a crucial role in calcium regulation within the sarcoplasmic reticulum (SR), a specialized type of endoplasmic reticulum in muscle cells. CASQ2 is essential for proper muscle function, particularly in the heart, where it helps maintain calcium homeostasis and supports the excitation-contraction coupling process .
CASQ2 is a high-capacity, low-affinity calcium-binding protein. Each molecule of CASQ2 can bind between 18 to 50 calcium ions, which it holds within the SR. This ability to store large amounts of calcium is vital for muscle contraction and relaxation cycles. The protein’s structure allows it to polymerize in response to changing calcium levels, enhancing its calcium-buffering capacity .
In the heart, CASQ2 is integral to the regulation of calcium release from the SR. It interacts with the ryanodine receptor (RyR2), the primary calcium release channel in cardiac muscle cells. By modulating RyR2 activity, CASQ2 helps ensure the precise timing and amount of calcium released during each heartbeat. This regulation is crucial for maintaining a regular heart rhythm and preventing arrhythmias .
Mutations in the CASQ2 gene have been linked to various cardiac disorders, including catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is a potentially life-threatening condition characterized by abnormal heart rhythms triggered by physical activity or emotional stress. These mutations can disrupt the normal function of CASQ2, leading to impaired calcium handling and increased susceptibility to arrhythmias .
Human recombinant CASQ2 is a laboratory-produced version of the protein, created using recombinant DNA technology. This technology allows for the production of large quantities of CASQ2, which can be used for research and therapeutic purposes. Recombinant CASQ2 is valuable for studying the protein’s function, understanding the mechanisms underlying related cardiac disorders, and developing potential treatments .