SARCOPLASMIC-RETICULUM CALSEQUESTRINS - STRUCTURAL AND FUNCTIONAL-PROPERTIES

Calsequestrin is the major Ca2+-binding protein localized in the termi nal cisternae of the sarcoplasmic reticulum (SR) of skeletal and cardi ac muscle cells. Calsequestrin has been purified and cloned from both skeletal and cardiac muscle in mammalian, amphibian, and avian species . Two different calsequestrin gene products namely cardiac and fast ha ve been identified. Fast and cardiac calsequestrin isoforms have a hig hly acidic amino acid composition. The amino acid composition of the c ardiac form is very similar to the skeletal form expect for the carbox yl terminal region of the protein which possess variable length of aci dic residues and two phosphorylation sites. Circular dichroism and NMR studies have shown that calsequestrin increases its alpha-helical con tent and the intrinsic fluorescence upon binding of Ca2+. Calsequestri n binds Ca2+ with high-capacity and with moderate affinity and its fun ctions as a Ca2+ storage protein in the lumen of the SR. Calsequestrin has been found to be associated with the Ca2+ release channel protein complex of the SR through protein-protein interactions. The human and rabbit fast calsequestrin genes have been cloned. The fast gene is sk eletal muscle specific and transcribed at different rates in fast and slow skeletal muscle but not in cardiac calsequestrin gene. This gene is also expressed in slow skeletal muscle. No change in calsequestrin mRNA expression has been detected in animal models of cardiac hypertro phy and in failing human heart.