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Inositol 1,4,5-Trisphosphate and Its Receptors

2012; Springer Nature; Linguagem: Inglês

10.1007/978-94-007-2888-2_11

2214-8019

Jan B. Parys, Humbert De Smedt,

Calcium signaling and nucleotide metabolism

Activation of cells by many extracellular agonists leads to the production of inositol 1,4,5-trisphosphate (IP3). IP3 is a global messenger that easily diffuses in the cytosol. Its receptor (IP3R) is a Ca2+-release channel located on intracellular membranes, especially the endoplasmic reticulum (ER). The IP3R has an affinity for IP3 in the low nanomolar range. A prime regulator of the IP3R is the Ca2+ ion itself. Cytosolic Ca2+ is considered as a co-agonist of the IP3R, as it strongly increases IP3R activity at concentrations up to about 300 nM. In contrast, at higher concentrations, cytosolic Ca2+ inhibits the IP3R. Also the luminal Ca2+ sensitizes the IP3R. In higher organisms three genes encode for an IP3R and additional diversity exists as a result of alternative splicing mechanisms and the formation of homo- and heterotetramers. The various IP3R isoforms have a similar structure and a similar function, but due to differences in their affinity for IP3, their variable sensitivity to regulatory parameters, their differential interaction with associated proteins, and the variation in their subcellular localization, they participate differently in the formation of intracellular Ca2+ signals and this affects therefore the physiological consequences of these signals.