ArticleThe Journal of biological chemistry2012
Glutamate 268 regulates transport probability of the anion/proton exchanger ClC-5.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Database ofKidney international reports · 2026Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.Human genetics · 2024Article
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon.Human genetics · 2021Review
- Large transient capacitive currents in wild-type lysosomal Cl-/H+ antiporter ClC-7 and residual transport activity in the proton glutamate mutant E312A.The Journal of general physiology · 2021Article
- Review
- Metabolic energy sensing by mammalian CLC anion/proton exchangers.EMBO reports · 2020Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- Barttin Regulates the Subcellular Localization and Posttranslational Modification of Human ClFrontiers in physiology · 2018Article
- ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.Frontiers in pharmacology · 2017Review
- Overexpression of the Endosomal Anion/Proton Exchanger ClC-5 Increases Cell Susceptibility towardFrontiers in cellular and infection microbiology · 2017Article
- Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions.The Journal of biological chemistry · 2015Article
- A tale of two CLCs: biophysical insights toward understanding ClC-5 and ClC-7 function in endosomes and lysosomes.The Journal of physiology · 2015Review
- Mutations associated with Dent's disease affect gating and voltage dependence of the human anion/proton exchanger ClC-5.Frontiers in physiology · 2015Article
- Multiple discrete transitions underlie voltage-dependent activation in CLC Cl(-)/H(+) antiporters.Biophysical journal · 2014Article
- Water access points and hydration pathways in CLC H+/Cl- transporters.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- ClC-3 is an intracellular chloride/proton exchanger with large voltage-dependent nonlinear capacitance.ACS chemical neuroscience · 2013Article
- On the mechanism of gating charge movement of ClC-5, a human Cl(-)/H(+) antiporter.Biophysical journal · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Cl(-)/H(+) exchange mediated by ClC transporters can be uncoupled by external SCN(-) and mutations of the proton glutamate, a conserved residue at the internal side of the protein. We show here for the mammalian ClC transporter ClC-5 that acidic internal pH led to a greater increase in currents upon exchanging extracellular Cl(-) for SCN(-). However, transport uncoupling, unitary current amplitudes, and the voltage dependence of the depolarization-induced activation were not altered by low pH values. Therefore, it is likely that an additional gating process regulates ClC-5 transport. Higher internal [H(+)] and the proton glutamate mutant E268H altered the ratio between ClC-5 transport and nonlinear capacitance, indicating that the gating charge movements in ClC-5 arise from incomplete transport cycles and that internal protons increase the transport probability of ClC-5. This was substantiated by site-directed sulfhydryl modification of the proton glutamate mutant E268C. The mutation exhibited small transport currents together with prominent gating charge movements. The charge restoration using a negatively charged sulfhydryl reagent reinstated also the WT phenotype. Neutralization of the charge of the gating glutamate 211 by the E211C mutation abolished the effect of internal protons, showing that the increased transport probability of ClC-5 results from protonation of this residue. S168P (a mutation that decreases the anion affinity of the central binding site) reduced also the internal pH dependence of ClC-5. These results support the idea that protonation of the gating glutamate 211 at the central anion-binding site of ClC-5 is mediated by the proton glutamate 268.
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