Calcium ion and signal transduction

Abstract

Ca²⁺ plays an important role in cell function. There are two mechanisms to regulate Ca²⁺ concentration inside the cell. One is through Ca² influx through Ca²⁺ channels on the plasma membrane. Another is Ca²⁺ release from internal store in side the cell. IP₃ is a second messenger to release Ca²⁺ from endoplasmic reticulum (ER) which is an intracellular store. We found that P400 protein deficient in Purkinje-neuron-degenerating mutant is IP₃ receptor (IP₃R). Studies on the role of IP₃R during development show that IP₃R is involved in fertilization and is essential for determination of dorsoventral axis formation. IP₃R is involved in neuronal plasticity. Double homozygous mutant of IP₃R2 and IP₃R3 shows deficit of saliva and pancreatic juice secretion. ERp44 works as a redox sensor in the ER and regulates IP₃R1 activity. We discovered that IP₃ not only releases Ca²⁺, but also releases IRBIT ( IP₃ receptor binding protein released with inositol trisphosphate). Since IRBIT binds to the IP₃ binding core in a phosphorylation dependent manner, IRBIT regulates IP3 induced Ca²⁺ release. In addition, IRBIT works as a third messenger to enchance pancreas type Na, Bicarbonate co-transporter 1 which regulates acid base balance of cells. And signaling pathway may be modified to be as follows: [signal →IP₃ →Ca²⁺ release] and [signal→IP₃ →IRBIT release →Na, Bicarbonate cotransporter 1 activation]. IP₃R is considered to work as a signaling center inside the cell by interacting with many molecules as “Calcio-signalsome”. [J Physiol Sci. 2007;57 Suppl:S2]