title: IP3receptor mutations and brain diseases in human and rodents.
abstract: The inositol 1,4,5-trisphosphate receptor (IP3R) is a huge Ca2+channel that is localized at the endoplasmic reticulum. The IP3R releases Ca2+from the endoplasmic reticulum upon binding to IP3, which is produced by various extracellular stimuli through phospholipase C activation. All vertebrate organisms have three subtypes of IP3R genes, which have distinct properties of IP3-binding and Ca2+sensitivity, and are differently regulated by phosphorylation and by their associated proteins. Each cell type expresses the three subtypes of IP3R in a distinct proportion, which is important for creating and maintaining spatially and temporally appropriate intracellular Ca2+level patterns for the regulation of specific physiological phenomena. Of the three types of IP3Rs, the type 1 receptor (IP3R1) is dominantly expressed in the brain and is important for brain function. Recent emerging evidence suggests that abnormal Ca2+signals from the IP3R1 are closely associated with human brain pathology. In this review, we focus on the recent advances in our knowledge of the regulation of IP3R1 and its functional implication in human brain diseases, as revealed by IP3R mutation studies and analysis of human disease-associated genes. This article is part of the mini review series "60th Anniversary of the Japanese Society for Neurochemistry".
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hisatsune
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium
keywords: Purkinje cell; calcium; disease; endoplasmic reticulum