Structure and Function of IP₃ Receptors

Inositol 1,4,5-trisphosphate receptors (IP₃Rs), by releasing Ca²⁺ from the endoplasmic reticulum (ER) of animal cells, allow Ca²⁺ to be redistributed from the ER to the cytosol or other organelles, and they initiate store-operated Ca²⁺ entry (SOCE). For all three IP₃R subtypes, binding of IP₃ primes them to bind Ca²⁺, which then triggers channel opening. We are now close to understanding the structural basis of IP₃R activation. Ca²⁺-induced Ca²⁺ release regulated by IP₃ allows IP₃Rs to regeneratively propagate Ca²⁺ signals. The smallest of these regenerative events is a Ca²⁺ puff, which arises from the nearly simultaneous opening of a small cluster of IP₃Rs. Ca²⁺ puffs are the basic building blocks for all IP₃-evoked Ca²⁺ signals, but only some IP₃ clusters, namely those parked alongside the ER-plasma membrane junctions where SOCE occurs, are licensed to respond. The location of these licensed IP₃Rs may allow them to selectively regulate SOCE.