ArticleThe Journal of biological chemistry2009
Putative re-entrant loop 1 of AE2 transmembrane domain has a major role in acute regulation of anion exchange by pH.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Structural and functional insights into the lipid regulation of human anion exchanger 2.Nature communications · 2024Article
- Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1.American journal of physiology. Cell physiology · 2021Review
- SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes.Cellular and molecular life sciences : CMLS · 2021Article
- Carbonic anhydrase IX and acid transport in cancer.British journal of cancer · 2020Review
- Microarray analysis reveals the inhibition of intestinal expression of nutrient transporters in piglets infected with porcine epidemic diarrhea virus.Scientific reports · 2019Article
- Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury.International journal of stem cells · 2019Article
- Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- VRACs and other ion channels and transporters in the regulation of cell volume and beyond.Nature reviews. Molecular cell biology · 2016Review
- Molecular cloning and functional characterization of zebrafish Slc4a3/Ae3 anion exchanger.Pflugers Archiv : European journal of physiology · 2014Article
- The chemistry, physiology and pathology of pH in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- 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
- Loss of Slc4a1b chloride/bicarbonate exchanger function protects mechanosensory hair cells from aminoglycoside damage in the zebrafish mutant persephone.PLoS genetics · 2012Article
- SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization.American journal of physiology. Cell physiology · 2011Article
- Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis.American journal of physiology. Cell physiology · 2011Article
- Loss of the AE3 anion exchanger in a hypertrophic cardiomyopathy model causes rapid decompensation and heart failure.Journal of molecular and cellular cardiology · 2011Article
- New insights into the physiological role of carbonic anhydrase IX in tumour pH regulation.Oncogene · 2010Review
- 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
- The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes.American journal of physiology. Cell physiology · 2010Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Normal pH sensitivity of the SLC4A2/AE2 anion exchanger requires transmembrane domain (TMD) amino acid (aa) residues not conserved in the homologous but relatively pH-insensitive SLC4A1/AE1 polypeptide. We tested the hypothesis that the nonconserved aa cluster 1075DKPK1078 within the first putative re-entrant loop (RL1) of AE2 TMD contributes to pH sensor function by studying anion exchange function of AE2 mutants in which these and other RL1 aa were systematically substituted with corresponding RL1 aa from AE1. Regulation of Cl-/Cl- and Cl-/HCO(-)3 exchange by intracellular pH (pHi) or extracellular pH (pHo) was measured as 4,4'-di-isothiocyanatostilbene-2,2' disulfonic acid-sensitive 36Cl- efflux from Xenopus oocytes. AE2 RL1 mutants 1075AAAQ1078 and 1075AAAQN1079 showed reduced pHi sensitivity and pHo sensitivity was acid-shifted by approximately 1 pH unit. Individual mutants D1075A and P1077A exhibited moderately altered pH sensitivity, whereas a range of substitutions at conserved AE2 Ile-1079 substantially altered sensitivity to pHo and/or pHi. Substitution of the complete AE1 RL1 with AE2 RL1 failed to confer AE2-like pH sensitivity onto AE1. Replacement, however, of AE1 RL1 763SGPGAAAQ770 with AE2 1071VAPGDKPK1078 restored pHi sensitivity to the chimera AE2(1-920)/AE1(613-929) without affecting its low sensitivity to pHo. The results show that acute regulation of AE2 by pH requires RL1 of the TMD. We propose that critical segments of RL1 constitute part of an AE2 pH sensor that, together with residues within the N-terminal half of the TMD, constrain the AE2 polypeptide in a conformation required for regulation of anion exchange by pHi.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.