Inositol 1,4,5-trisphosphate receptors (IP3Rs) are large proteins that play an important role in linking the many receptors. They are also important in mediating the regenerative propagation of intracellular Ca2+ signals by means of Ca2+-induced Ca2+ release. IP3Rs are thus responsible for initiating and sustaining Ca2+ signals, and interactions between IP3Rs determine whether Ca2+ signals are local or global. Key structural features of a single subunit of the type 1 IP3R are shown in this chapter. Many additional pathways modulate iP3Rs. ATP binds to sites within the modulatory domain and increases IP3 sensitivity, but its effects differ profoundly between IP3R subtypes. Most IP3Rs are found in the membranes of the ER, but they also occur in the Golgi apparatus, secretory vesicles, nuclear envelope, and plasma membrane. The modulation of Ca2+ signals by many addition signals and association with many different proteins allows them effectively to integrate diverse signals before returning them to the cell as a Ca2+ signal.
