Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs

Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are expressed in nearly all animal cells, where they mediate the release of Ca2+ from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca2+ signals allows selective regulation of diverse physiological responses. Interactions of IP(3)Rs with other proteins contribute to the specificity and speed of Ca2+ signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP(3)Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP(3)Rs, facilitate their regulation by multiple signalling pathways and direct the Ca2+ that they release to specific targets. We suggest that IP(3)Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca2+ signals.