Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger

被引：58

作者：

Alexander, Robert Todd ^{[1
,2
]}

Jaumouille, Valentin ^{[1
]}

Yeung, Tony ^{[1
]}

Furuya, Wendy ^{[1
]}

Peltekova, Iskra ^{[1
]}

Boucher, Annie ^{[3
]}

Zasloff, Michael ^{[4
]}

Orlowski, John ^{[3
]}

Grinstein, Sergio ^{[1
,5
]}

机构：

[1] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada

[2] Univ Alberta, Dept Pediat, Edmonton, AB, Canada

[3] McGill Univ, Dept Physiol, Montreal, PQ, Canada

[4] Georgetown Univ, Dept Surg, Washington, DC USA

[5] Univ Toronto, Dept Biochem, Toronto, ON, Canada

来源：

EMBO JOURNAL | 2011年 / 30卷 / 04期

关键词：

Na+/H+ exchange; pH regulation; surface charge; THICK ASCENDING LIMB; C-TERMINAL DOMAINS; PLASMA-MEMBRANE; NHE3; ACTIVITY; BRUSH-BORDER; HCO3-ABSORPTION; ATP DEPENDENCE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; CA2+-DEPENDENT INHIBITION; APICAL MEMBRANE;

D O I：

10.1038/emboj.2010.356

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 Na+/H+ exchanger NHE3 plays a central role in intravascular volume and acid-base homeostasis. Ion exchange activity is conferred by its transmembrane domain, while regulation of the rate of transport by a variety of stimuli is dependent on its cytosolic C-terminal region. Liposome-and cell-based assays employing synthetic or recombinant segments of the cytosolic tail demonstrated preferential association with anionic membranes, which was abrogated by perturbations that interfere with electrostatic interactions. Resonance energy transfer measurements indicated that segments of the C-terminal domain approach the bilayer. In intact cells, neutralization of basic residues in the cytosolic tail by mutagenesis or disruption of electrostatic interactions inhibited Na+/H+ exchange activity. An electrostatic switch model is proposed to account for multiple aspects of the regulation of NHE3 activity. The EMBO Journal (2011) 30, 679-691. doi:10.1038/emboj.2010.356; Published online 18 January 2011

引用

页码：679 / 691

页数：13

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