IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor

被引：132

作者：

Ando, Hideaki ^{[1
]}

Mizutani, Akihiro ^{[1
]}

Kiefer, Hélène ^{[1
]}

Tsuzurugi, Dai ^{[1
]}

Michikawa, Takayuki ^{[1
]}

Mikoshiba, Katsuhiko ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Div Mol Neurobiol, Tokyo 1088639, Japan

来源：

MOLECULAR CELL | 2006年 / 22卷 / 06期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

D O I：

10.1016/j.molcel.2006.05.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The inositol 1,4,5-trisphosphate (IP3) receptors (IP(3)Rs) are IP3-gated intracellular Ca2+ channels. We previously identified an IP3R binding protein, IRBIT, which binds to the IP3 binding domain of IP3R and is dissociated from IP3R in the presence of IP3- In the present study, we showed that IRBIT suppresses the activation of IP3R by competing with IP3 by [H-3]IP3 binding assays, in vitro Ca2+ release assays, and Ca2+ imaging of intact cells. Multiserine phosphorylation of IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for IP3 recognition participated in binding to IRBIT. We propose a unique mode of IP3R regulation in which IP3 sensitivity is regulated by IRBIT acting as an endogenous "pseudoligand" whose inhibitory activity can be modulated by its phosphorylation status.

引用

页码：795 / 806

页数：12

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