Subcellular distribution of the inositol 1,4,5-trisphosphate receptors: functional relevance and molecular determinants.

The inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca^2+ channel that is for the largest part expressed in the endoplasmic reticulum. Its precise subcellular localization is an important factor for the correct initiation and propagation of Ca^2+ signals. The relative position of the IP3Rs, and thus of the IP3-sensitive Ca^2+ stores, to mitochondria, nucleus or plasma membrane determines in many cases the physiological consequences of IP3-induced Ca^2+ release. Most cell types express more than one IP3R isoform and their subcellular distribution is cell-type dependent. Moreover, it was recently demonstrated that depending on the physiological status of the cell redistribution of IP3Rs and/or of IP3-sensitive Ca^2+ stores could occur. This indicates that the cell must be able to regulate not only IP3R expression but also its distribution. The various proteins potentially determining IP3R localization and redistribution will therefore be discussed.