Article

Inositol Trisphosphate Receptor Ca2+ Release Channels

Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085, USA.
Physiological Reviews (Impact Factor: 27.32). 05/2007; 87(2):593-658. DOI: 10.1152/physrev.00035.2006
Source: PubMed

ABSTRACT

The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.

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    • "ctly or indirectly ( Fiacco and McCarthy , 2006 ) . There is also a wealth of research demonstrating crosstalk between the cal - cium signaling apparatus and other second messenger signal - ing networks ( Bruce et al . , 2003 ; Clementi and Meldolesi , 1997 ) , perhaps best exemplified by the range of signals that converge on the InsP 3 receptor ( Foskett et al . , 2007 ) . This suggests that coincident activation of neurotransmitter recep - tors coupled to calcium release and modulatory receptors coupled to pathways that affect calcium signaling could alter the probability of generating a global calcium response . Endocannabinoid signaling mediates neuromodulation in many neuronal classes and many bra"
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    • "The basic structure of IP3Rs has two major sites of homology between the subtypes: the N-terminal region with the binding site for IP3 (Mignery and Sudhof 1990; Sudhof et al. 1991; Yoshikawa et al. 1996) and the C-terminus with the channel domain and the tetramer formation determinants (Michikawa et al. 1994; Boehning et al. 2001). The central modulatory or coupling domain that contains several interaction sites for many intracellular regulators and interacting proteins is the intervening domain (~1700 a. a.) that exhibits more sequence variability between subtypes (Missiaen et al. 1992a; Patterson and Boehning 2004; Bezprozvanny 2005; Mikoshiba 2007a, 2007b; Foskett et al. 2007). By far, the largest amount of information about regulatory mechanisms is available for IP3R1, while the other subtypes are less extensively documented . "

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