Calsequestrin is a calcium-binding protein that acts as a calcium buffer within the sarcoplasmic reticulum. The protein helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle contraction, even though the concentration of calcium in the sarcoplasmic reticulum is much higher than in the cytosol. It also helps the sarcoplasmic reticulum store an extraordinarily high amount of calcium ions. Each molecule of calsequestrin can bind 18 to 50 Ca2+ ions. Sequence analysis has suggested that calcium is not bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrin have been identified. The cardiac form Calsequestrin-2 (CASQ2) is present in cardiac and slow skeletal muscle and the fast skeletal form Calsequestrin-1(CASQ1) is found in fast skeletal muscle. The release of calsequestrin-bound calcium (through a calcium release channel) triggers muscle contraction. The active protein is not highly structured, more than 50% of it adopting a random coil conformation. When calcium binds there is a structural change whereby the alpha-helical content of the protein increases from 3 to 11%. Both forms of calsequestrin are phosphorylated by casein kinase 2, but the cardiac form is phosphorylated more rapidly and to a higher degree. Calsequestrin is also secreted in the gut where it deprives bacteria of calcium ions.
Background References
1. Zhang L et al. Calsequestrin-1 regulates store-operated Ca2+ entry by inhibiting STIM1 aggregation. Cell Physiol Biochem 38:2183-2193 (2016).
2. Sanchez E J et al. High-capacity Ca2+ binding of human skeletal calsequestrin. J Biol Chem 287:11592-11601 (2012).
Immunohistochemical analysis of paraffin-embedded rat skeletal muscle tissue using anti-Calsequestrin 1 antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded human fetal skeletal muscle tissue using anti-Calsequestrin 1 antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded mouse skeletal muscle tissue using anti-Calsequestrin 1 antibody. Counter stained with hematoxylin.
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