Inositol 1,4,5-Trisphosphate and Its Receptors

Abstract

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 Ca(2+)-release channel located on intracellular membranes, especially the endoplasmic reticulum (ER). The IP₃R has an affinity for IP(3) in the low nanomolar range. A prime regulator of the IP₃R is the Ca(2+) ion itself. Cytosolic Ca(2+) is considered as a co-agonist of the IP₃R, as it strongly increases IP(3)R activity at concentrations up to about 300 nM. In contrast, at higher concentrations, cytosolic Ca(2+) inhibits the IP₃R. Also the luminal Ca(2+) 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 Ca(2+) signals and this affects therefore the physiological consequences of these signals.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…The involvement of PLC in UT signaling has been confirmed in cultured rat cortical astrocytes (Castel et al, 2006;Jarry et al, 2010). IP 3 binds to the IP 3 receptor, a calcium channel on the membrane of the endoplasmic reticulum, resulting in an increase in cytoplasmic calcium levels (Parys and de Smedt, 2012) (Fig. 9B).…”

The type 2 inositol 1,4,5-trisphosphate receptor, emerging functions for an intriguing Ca2+-release channel

“…These proteins include regulatory and structural proteins, many of which were also reported to interact with IP 3 R1 and/or IP 3 R3 [1, 2, 14]. An interesting exception is the interaction described between IP 3 R2 and type 6 adenylate cyclase (AC6) [113].…”

Architecture and conformational switch mechanism of the ryanodine receptor

“…RyRs share structural and sequence homology with another important calcium channel, the inositol-1,4,5-triphosphate receptor (Ins(1,4,5)P 3 or IP 3 receptor) 6 . IP 3 receptors reside in the endoplasmic reticulum and form a part of the intracellular signalling system converting external stimuli into calcium signals 7 . More than 300 mutations in RyRs have been associated with human diseases, including malignant hyperthermia, fatal cardiac arrhythmias, cardiac sudden death and neurological disorders 3,8,9 .…”