The InsP3 receptor and intracellular Ca2+ signaling

doi:10.1016/S0959-4388(97)80061-X

Current Opinion in Neurobiology

Volume 7, Issue 3, June 1997, Pages 339-345

https://doi.org/10.1016/S0959-4388(97)80061-X Get rights and content

Abstract

The inositol 1,4,5-trisphosphate receptor (InsP₃R) 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 (InsP₃) to InsP₃R isoforms is differentially regulated by Ca²⁺, and that InsP₃R 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 InsP₃R for capacitative Ca²⁺ entry. The importance of InsP₃R 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.

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Citation Excerpt :
Although it is not fully established how Ca2+ coordinates such diverse functions, there is evidence that they may be regulated by the spatial patterns of Ca2+ distribution [1]. The rise in intracellular Ca2+ levels can occur through the generation of inositol 1,4,5-trisphosphate (InsP3), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by phospholipases C (PLCs), leading to Ca2+ release by InsP3 receptors (InsP3R) present in the membrane of the endoplasmic reticulum [5, 6]. In turn, Ca2+ activates sensor molecules, like calmodulin, which modulate cellular activity [7].
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The InsP3 receptor and intracellular Ca2+ signaling

Abstract

Curr Opin Neurobiol

J Biol Chem

Trends Pharmacol Sci

J Biol Chem

J Biol Chem

Biochem Biophys Res Commun

Neuron

Biochem J

Am J Physiol

FEBS Lett

J Biol Chem

J Biol Chem

Cell

J Biol Chem

Proc Acad Natl Sci USA

J Biol Chem

J Biol Chem

Bioorg Med Chem Lett

Biochem Biophys Res Commun

Am J Physiol

Am J Physiol

Cell

Proc Natl Acad Sci USA

Cell

Science

Dev Biol

J Cell Biol

J Cell Biol

J Cell Biol

Nature

J Neurosci

Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400

Nature

Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues

Proc Natl Acad Sci USA

Mechanisms responsible for quantal Ca2+ release from inositol trisphosphate-sensitive calcium stores

Eur J Physiol

The inositol 1,4,5-trisphosphate receptor binding sites of platelet membranes

Biochem J

The InsP₃ receptor and intracellular Ca²⁺ signaling

Mechanisms responsible for quantal Ca²⁺ release from inositol trisphosphate-sensitive calcium stores