The InsP(3) receptor and intracellular Ca2+ signaling

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is a ligand-gated Ca2+-release channel on intracellular Ca2+ store sites (such as the endoplasmic reticulum), and plays an important role in intracellular Ca2+ signaling in a wide variety of cell types. Recent studies have shown that binding of inositol 1,4,5-trisphosphate (InsP(3)) to InsP(3)R isoforms is differentially regulated by Ca2+, and that InsP(3)R functions are finely regulated by phosphorylation via tyrosine kinases and protein kinase C, by dephosphorylation via calcineurin, and by binding to FKBP (FK506-binding protein). In addition, transient receptor potential (TRP) and TRP-like proteins appear to couple conformationally with the InsP(3)R for capacitative Ca2+ entry. The importance of InsP(3)R signaling in neuronal function has been demonstrated by gene targeting in mice and by studies of T-cell receptor signaling, apoptosis, meiotic maturation, and cytokinesis.