Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pflugers Arch
2007 Jun 01;4543:373-84. doi: 10.1007/s00424-007-0220-8.
Show Gene links
Show Anatomy links
Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH.
Stewart AK
,
Kurschat CE
,
Alper SL
.
???displayArticle.abstract???
The ubiquitous AE2/SLC4A2 anion exchanger is acutely and independently regulated by intracellular (pH(i)) and extracellular pH (pH(o)), whereas the closely related AE1/SLC4A1 of the red cell and renal intercalated cell is relatively pH-insensitive. We have investigated the contribution of nonconserved charged residues within the C-terminal transmembrane domain (TMD) of AE2 to regulation by pH through mutation to the corresponding AE1 residues. AE2-mediated Cl(-)/Cl(-) exchange was measured as 4,4'-di-isothiocyanatostilbene-2,2'-disulfonic acid-sensitive (36)Cl(-) efflux from Xenopus oocytes by varying pH(i) at constant pH(o), and by varying pH(o) at near-constant pH(i). All mutations of nonconserved charged residues of the AE2 TMD yielded functional protein, but mutations of some conserved charged residues (R789E, R1056A, R1134C) reduced or abolished function. Individual mutation of AE2 TMD residues R921, F922, P1077, and R1107 exhibited reduced pH(i) sensitivity compared to wt AE2, whereas TMD mutants K1153R, R1155K, R1202L displayed enhanced sensitivity to acidic pH(i). In addition, pH(o) sensitivity was significantly acid- shifted when nonconserved AE2 TMD residues E981, K982, and D1075 were individually converted to the corresponding AE1 residues. These results demonstrate that multiple conserved charged residues are important for basal transport function of AE2 and that certain nonconserved charged residues of the AE2 TMD are essential for wild-type regulation of anion exchange by pH(i) and pH(o).
Abuladze,
Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.
2005, Pubmed
Abuladze,
Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.
2005,
Pubmed
Accardi,
Ionic currents mediated by a prokaryotic homologue of CLC Cl- channels.
2004,
Pubmed
Alper,
The AE gene family of Cl/HCO3- exchangers.
2002,
Pubmed
Aubin,
Positive charges at the intracellular mouth of the pore regulate anion conduction in the CFTR chloride channel.
2006,
Pubmed
Bénitah,
Proton inhibition of sodium channels: mechanism of gating shifts and reduced conductance.
1997,
Pubmed
,
Xenbase
Bruce,
Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.
2005,
Pubmed
,
Xenbase
Chanchevalap,
Involvement of histidine residues in proton sensing of ROMK1 channel.
2000,
Pubmed
Chernova,
Functional consequences of mutations in the transmembrane domain and the carboxy-terminus of the murine AE1 anion exchanger.
1997,
Pubmed
,
Xenbase
Choe,
A conserved cytoplasmic region of ROMK modulates pH sensitivity, conductance, and gating.
1997,
Pubmed
,
Xenbase
Coric,
Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel.
2005,
Pubmed
Dahlmann,
Regulation of Kir channels by intracellular pH and extracellular K(+): mechanisms of coupling.
2004,
Pubmed
,
Xenbase
Dominguez,
Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos.
1995,
Pubmed
,
Xenbase
Fakler,
Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.
1996,
Pubmed
,
Xenbase
Fujinaga,
Topology of the membrane domain of human erythrocyte anion exchange protein, AE1.
1999,
Pubmed
Funder,
Chloride transport in human erythrocytes and ghosts: a quantitative comparison.
1976,
Pubmed
Gawenis,
Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric.
2004,
Pubmed
Grinstein,
Anion transport in relation to proteolytic dissection of band 3 protein.
1978,
Pubmed
Horita,
Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
2005,
Pubmed
,
Xenbase
Humphreys,
Functional characterization and regulation by pH of murine AE2 anion exchanger expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Karbach,
Effect of site-directed mutagenesis of the arginine residues 509 and 748 on mouse band 3 protein-mediated anion transport.
1998,
Pubmed
,
Xenbase
Khan,
Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block.
2002,
Pubmed
,
Xenbase
Kopito,
Primary structure and transmembrane orientation of the murine anion exchange protein.
,
Pubmed
Kopito,
Regulation of intracellular pH by a neuronal homolog of the erythrocyte anion exchanger.
1989,
Pubmed
Li,
Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis.
2005,
Pubmed
,
Xenbase
Linsdell,
Mechanism of chloride permeation in the cystic fibrosis transmembrane conductance regulator chloride channel.
2006,
Pubmed
Morton,
pH sensing in the two-pore domain K+ channel, TASK2.
2005,
Pubmed
Picollo,
Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5.
2005,
Pubmed
Romero,
The SLC4 family of HCO 3 - transporters.
2004,
Pubmed
Scheel,
Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins.
2005,
Pubmed
,
Xenbase
Schulte,
pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome.
1999,
Pubmed
Stewart,
Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain.
2002,
Pubmed
,
Xenbase
Stewart,
Acute pH-dependent regulation of AE2-mediated anion exchange involves discrete local surfaces of the NH2-terminal cytoplasmic domain.
2004,
Pubmed
,
Xenbase
Stewart,
Transmembrane domain histidines contribute to regulation of AE2-mediated anion exchange by pH.
2007,
Pubmed
,
Xenbase
Stewart,
Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain.
2001,
Pubmed
,
Xenbase
Toye,
The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia.
2006,
Pubmed
,
Xenbase
Wakabayashi,
Mutations of Arg440 and Gly455/Gly456 oppositely change pH sensing of Na+/H+ exchanger 1.
2003,
Pubmed
Zhang,
The cytoplasmic and transmembrane domains of AE2 both contribute to regulation of anion exchange by pH.
1996,
Pubmed
,
Xenbase
Zhu,
Novel topology in C-terminal region of the human plasma membrane anion exchanger, AE1.
2003,
Pubmed
Zhu,
The substrate anion selectivity filter in the human erythrocyte Cl-/HCO3- exchange protein, AE1.
2004,
Pubmed
