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

Abstract

Inositol 1,4,5‐trisphosphate receptors (IP ₃Rs) are expressed in nearly all animal cells, where they mediate the release of Ca ²⁺ from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca ²⁺ signals allows selective regulation of diverse physiological responses. Interactions of IP ₃Rs with other proteins contribute to the specificity and speed of Ca ²⁺ 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 ₃Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP ₃Rs, facilitate their regulation by multiple signalling pathways and direct the Ca ²⁺ that they release to specific targets. We suggest that IP ₃Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca ²⁺ signals.