RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity

被引：31

作者：

Onishi, Ichiro ^{[1
]}

Lin, Paulo J. C. ^{[1
]}

Diering, Graham H. ^{[1
]}

Williams, Warren P. ^{[1
]}

Numata, Masayuki ^{[1
]}

机构：

[1] Univ British Columbia, Biomed Res Ctr, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada

来源：

CELLULAR SIGNALLING | 2007年 / 19卷 / 01期

基金：

加拿大健康研究院;

关键词：

ion homeostasis; scaffold signaling proteins; protein-protein interaction; focal adhesion;

D O I：

10.1016/j.cellsig.2006.06.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Na+/H+ exchanger isoform 5 (NHE5) is a brain-enriched NHE that may play important roles in ion homeostasis and cell-volume regulation. However, the regulation mechanism of NHE5 has not been fully elucidated. Here, we show that Receptor for Activated C-kinase 1 (RACK1) directly binds to NHE5 and positively regulates the transporter function. NHE5 co-localized with RACK1 as well as beta 1 integrin, paxillin and vinculin, suggesting that NHE5 associates with focal adhesions. By using RACK1 dominant-negative mutants and siRNA, we further show that RACK1 regulates NHE5 both directly and through an integrin-dependent pathway. The NHE5-RACK1 interaction, but not the RACK1-beta 1 integrin interaction, was reinforced when cells were spread on an integrin-substrate fibronectin. We propose that RACK1 activates NHE5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：194 / 203

页数：10