Molecular properties of inositol 1,4,5-trisphosphate receptors

The receptors for the second messenger inositol 1,4,5-trisphosphate (IP3) c onstitute a family of Ca2+ channels responsible for the mobilization of int racellular Ca2+ stores. Three different gene products (types I-III) have be en isolated, encoding polypeptides which assemble as large tetrameric struc tures. Recent molecular studies have advanced our knowledge about the struc ture, regulation and function of IP3 receptors. For example, several Ca2+-b inding sites and a Ca2+-calmodulin-binding domain have been mapped within t he type I IP3 receptor, and studies on purified cerebellar IP3 receptors pr opose a second Ca2+-independent calmodulin-binding domain. In addition, min imal requirements for the binding of immunophilins and the formation of tet ramers have been identified. Overexpression of IP3 receptors has provided f urther clues to the regulation of individual IP3 receptor isoforms present within cells, and the role that they play in the generation of IP3-dependen t Ca2+ signals. Inhibition of IP3 receptor function and expression, and ana lysis of mutant IP3 receptors, suggests that IP3 receptors are involved in such diverse cellular processes as proliferation and apoptosis and are thus , necessary for normal development. Our understanding of the complex spatia l and temporal nature of cytosolic Ca2+ increases and the role that these C a2+ signals play in cell function depend upon our knowledge of the structur e and the regulation of IP3 receptors. This review focuses on the molecular properties of these ubiquitous intracellular Ca2+ channels.