Structure and Function of Inositol 1,4,5-Trisphosphate Receptor.

Abstract

ABSTRACT-Generationof intracellular Ca2+ signals in response to Ca2+ -mobilizing stimuli is a critical event in the control of many cellular processes. Inositol 1,4,5-trisphosphate (IP3) represents a dominant second messenger subserving the release of Ca2+ from intracellular store sites. The protein on the surface of which the IP3 receptor is located comprises an IP3-gated Ca2+ channel, and binding of IP3 to this receptor triggers the release of Ca2+ through this channel. The receptor for IP3 displays a close resemblance to the ryanodine receptor, another intracellular Ca2+ channel, in many molecular and physiological properties. Many lines of evidence strongly suggest the central role that the IP3 receptor plays in the conversion of numerous external stimuli to intracellular Ca2+ signals characterized by complex spatiotemporal patterns such as Ca2+ waves and oscillations. In this review, we shall summarize our current knowledge of the structure and function of the IP3 receptor in order to understand the way how the activity of this important receptor is regulated to accomodate itself to the generation of diverse intracellular Ca2+ signals.

Inositol Trisphosphate Receptor Ca2+Release Channels

“…The InsP 3 Rs are ϳ2,700 -2,800 amino acid intracellular membrane proteins that exist as homo-or heterotetramers (209,210,212,270,311,328,363,443,536). By analogy with other cation channels and some structural information, the ion-conducting pore is believed to be created at the central axis of the tetrameric structure (Fig.…”

Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle

“…There are three genes that encode InsP 3 R and also three genes that encode RyR, each generating a specific isoform. The sequences encoded by InsP 3 R and RyR genes house a basic similarity in structure, sharing fragmental amino acid residue homology concentrated in the ligand-binding and Ca 2ϩ channel domains, implying fundamental roles of these domains in the activity of the SR Ca 2ϩ channels (Yoshida and Imai, 1997) and suggesting a common ancestral history (Sorrentino and Rizzuto, 2001). Each of these release channels is indeed configured in as a tetrameric formation, with the RyR being homotetrameric, the InsP 3 R being heterotetrameric, and the molecular weights of purified InsP 3 R (500 kDa) and RyR (300 kDa) indicating large protein structures (Furuichi et al, 1989(Furuichi et al, , 1994.…”

A dynamic model of the type-2 inositol trisphosphate receptor

“…One of the most important of these mechanisms is the inositol trisphosphate receptor (IPR), which also functions as a Ca 2ϩ channel. There is now a great deal of experimental evidence that in many cell types, oscillations and waves of Ca 2ϩ are mediated in major part by the release through the IPR of Ca 2ϩ from the endoplasmic reticulum, and that it is the modulation of the IPR by Ca 2ϩ and by inositol (1,4,5)-trisphosphate (IP 3 ) that causes such complex dynamic behavior (1)(2)(3)(4)(5)(6)(7).…”