Structure and function of ip3 receptors

Abstract

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.