REGULATION OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS

Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a soluble second messen ger responsible for the generation of highly organized Ca2+ signals in a variety of cell types. These Ca2+ signals control many cellular res ponses, including cell growth, fertilization, smooth muscle contractio n and secretion. Ins(1,4,5)P3 is produced at the plasma membrane follo wing receptor activation, but rapidly diffuses into the cytosol, where it binds to specific receptors through which it mobilizes intracellul ar Ca2+ stores. The actions of Ins(1,4,5)P3 within cells are tightly c ontrolled: enzymes control the rapid generation and metabolism of Ins( 1,4,5)P3 following receptor activation; multiple Ins(1,4,5)P3 receptor subtypes and splice variants exist, some of which are differentially expressed between cell types and at different stages of development; a nd Ins(1,4,5)P3 receptors are the targets for a number of allosteric r egulators, including protein kinases, ATP and divalent cations. Unders tanding how cells control the Ca2+-mobilizing activity of Ins(1,4,5)P3 will be important if we are to unravel the mechanisms that underlie t he complex arrangements of Ca2+ signals.