Structure and Function of IP Receptors.

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