Calexcitin B Is a New Member of the Sarcoplasmic Calcium-binding Protein Family

Calexcitin (CE) is a calcium sensor protein that has been implicated in associative learning. The CE gene was previously cloned from the long-finned squid, Loligo pealei, and the gene product was shown to bind GTP and modulate K⁺ channels and ryanodine receptors in a Ca²⁺-dependent manner. We cloned a new gene from L. pealei, which encodes a CE-like protein, here named calexcitin B (CE_B). CE_B has 95% amino acid identity to the original form. Our sequence analyses indicate that CEs are homologous to the sarcoplasmic calcium-binding protein subfamily of the EF-hand superfamily. Far and near UV circular dichroism and nuclear magnetic resonance studies demonstrate that CE_B binds Ca²⁺ and undergoes a conformational change. CE_B is phosphorylated by protein kinase C, but not by casein kinase II. CE_B does not bind GTP. Western blot experiments using polyclonal antibodies generated against CE_B showed that CE_B is expressed in the L. pealei optic lobe. Taken together, the neuronal protein CE represents the first example of a Ca²⁺ sensor in the sarcoplasmic calcium-binding protein family.