Calcium Signaling

 Calcium ion is an important second messenger involved in cell signaling and signal transduction. Most calcium in cells is sequestered in intracellular vesicles, the endoplasmic reticulum (ER) or mitochondria, where it is stored for release when needed. Small, localized increases in calcium result from its regulated release from the ER, which is produced by inositol trisphosphate, IP₃. IP₃ is produced by the hormone-dependent hydrolysis of phosphoinositides, to produce inositol phosphates, including IP₃. The IP₃ binds to a specific ER protein, a specialized calcium channel with four identical subunits, each with a single membrane-spanning segment and a single IP₃-binding site (1). The binding of IP₃ to this receptor results in a stereospecific release of calcium from the ER.

IP₃-sensitive calcium channels are expressed ubiquitously in tissues. However, the process of regulated calcium release is most tightly regulated in endocrine and neuronal cells, and it is often involved in coupling stimulus to secretion, which is usually a calcium-dependent process. Calcium release from the ER is oscillatory in nature. Increases in intracellular calcium are modulated not by increases in the amount of the ion released, but instead by the frequency of the oscillations. This may explain why the release of some hormones is pulsatile.

One of the critical targets in calcium signaling is CAM kinase, a multigene family of protein kinases that are sensitive to regulation by calcium/calmodulin. There are at least four members of this protein kinase family, with differences in distribution and substrate specificity. CAM kinases appear to be especially critical to modulation of signaling in the central nervous system (2).

References

1. M. J. Berridge (1993) Nature 361, 315–325. 

2. P. I. Hanson and H. Shulman (1992) Annu. Rev. Biochem. 61, 229–601.