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

共 54 条

[1] Intracellular pH regulation by Na+/H+ exchange requires phosphatidylinositol 4,5-bisphosphate [J].

Aharonovitz, O ;

Zaun, HC ;

Balla, T ;

York, JD ;

Orlowski, J ;

Grinstein, S .

JOURNAL OF CELL BIOLOGY, 2000, 150 (01) :213-224

[2] ATP dependence is not an intrinsic property of Na+/H+ exchanger NHE1:: requirement for an ancillary factor [J].

Aharonovitz, O ;

Demaurex, N ;

Woodside, M ;

Grinstein, S .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1999, 276 (06) :C1303-C1311

[3] C-terminal domains of Na+/H+ exchanger isoform 3 are involved in the basal and serum-stimulated membrane trafficking of the exchanger [J].

Akhter, S ;

Cavet, ME ;

Tse, CM ;

Donowitz, M .

BIOCHEMISTRY, 2000, 39 (08) :1990-2000

[4] Squalamine, a novel cationic steroid, specifically inhibits the brush-border Na+/H+ exchanger isoform NHE3 [J].

Akhter, S ;

Nath, SK ;

Tse, CM ;

Williams, J ;

Zasloff, M ;

Donowitz, M .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1999, 276 (01) :C136-C144

[5] Na+/H+ exchangers and the regulation of volume [J].

Alexander, R. T. ;

Grinstein, S. .

ACTA PHYSIOLOGICA, 2006, 187 (1-2) :159-167

[6] Membrane curvature alters the activation kinetics of the epithelial Na+/H+ exchanger, NHE3 [J].

Alexander, R. Todd ;

Malevanets, Anatoly ;

Durkan, Anne M. ;

Kocinsky, Hetal S. ;

Aronson, Peter S. ;

Orlowski, John ;

Grinstein, Sergio .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (10) :7376-7384

[7] Rho GTPases dictate the mobility of the Na/H exchanger NHE3 in epithelia:: Role in apical retention and targeting [J].

Alexander, RT ;

Furuya, W ;

Szászi, K ;

Orlowski, J ;

Grinstein, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (34) :12253-12258

[8]

Cabado AG, 1996, J BIOL CHEM, V271, P3590

[9] The NHE3 juxtamembrane cytoplasmic domain directly binds ezrin: Dual role in NHE3 trafficking and mobility in the brush border [J].

Cha, Boyoung ;

Tse, Ming ;

Yun, Chris ;

Kovbasnjuk, Olga ;

Mohan, Sachin ;

Hubbard, Ann ;

Arpin, Monique ;

Donowitz, Mark .

MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (06) :2661-2673

[10] The lateral mobility of NHE3 on the apical membrane of renal epithelial OK cells is limited by the PDZ domain proteins NHERF1/2, but is dependent on an intact actin cytoskeleton as determined by FRAP [J].

Cha, BY ;

Kenworthy, A ;

Murtazinal, R ;

Donowitz, M .

JOURNAL OF CELL SCIENCE, 2004, 117 (15) :3353-3365

← 1 2 3 4 5 6 →