Bi-directional signalling from the InsP3 receptor: regulation by calcium and accessory factors

Calcium is a pleiotropic messenger controlling a diverse array of intracellular events from fertilization to cell death. One of the main mechanisms by which intracellular calcium is elevated is through InsP₃ [Ins(1,4,5)P₃]-induced mobilization of calcium from its receptor on the endoplasmic reticulum calcium store. The activity of the InsP₃R (InsP₃ receptor) is subject to regulation by many factors other than InsP₃, most notably calcium itself, which regulates the channel in a bell-shaped dependent manner. InsP₃R sensitivity is also regulated by post-translational modifications such as phosphorylation and by binding of accessory proteins. Taken together it appears that the InsP₃R can be regarded as a cellular sensor for many signalling pathways, qualitatively and quantitatively regulating intracellular calcium signals with consequences for downstream cellular physiology.