ArticlePflugers Archiv : European journal of physiology2007
Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH.
Article in Pflugers Archiv : European journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
- Structural and functional insights into the lipid regulation of human anion exchanger 2.Nature communications · 2024Article
- Structure and Function of SLC4 Family [Formula: see text] Transporters.Frontiers in physiology · 2015Article
- Molecular cloning and functional characterization of zebrafish Slc4a3/Ae3 anion exchanger.Pflugers Archiv : European journal of physiology · 2014Article
- Substitution of transmembrane domain Cys residues alters pH(o)-sensitive anion transport by AE2/SLC4A2 anion exchanger.Pflugers Archiv : European journal of physiology · 2013Article
- SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis.American journal of physiology. Cell physiology · 2011Article
- Role of an extracellular loop in determining the stoichiometry of Na+-HCO₃⁻ cotransporters.The Journal of physiology · 2011Article
- A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Article
- Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer.Journal of cancer research and clinical oncology · 2009Article
- CO2-induced ion and fluid transport in human retinal pigment epithelium.The Journal of general physiology · 2009Article
- Putative re-entrant loop 1 of AE2 transmembrane domain has a major role in acute regulation of anion exchange by pH.The Journal of biological chemistry · 2009Article
- Mouse Ae1 E699Q mediates SO42-i/anion-o exchange with [SO42-]i-dependent reversal of wild-type pHo sensitivity.American journal of physiology. Cell physiology · 2008Article
- Acute regulation of mouse AE2 anion exchanger requires isoform-specific amino acid residues from most of the transmembrane domain.The Journal of physiology · 2007Article
- Identification of multiple substrate binding sites in SLC4 transporters in the outward-facing conformation: Insights into the transport mechanism.The Journal of biological chemistryArticle
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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).
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