ArticleBiophysical journal2012
On the mechanism of gating charge movement of ClC-5, a human Cl(-)/H(+) antiporter.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Dominant Action ofCells · 2025Article
- Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease.PNAS nexus · 2025Article
- Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023Article
- Biophysical Aspects of Neurodegenerative and Neurodevelopmental Disorders Involving Endo-/Lysosomal CLC ClLife (Basel, Switzerland) · 2023Review
- The Role of the Lysosomal ClCells · 2022Review
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.American journal of human genetics · 2021Article
- Not so transport incompetent after all: Revisiting a CLC-7 mutant sheds new mechanistic light on lysosomal physiology.The Journal of general physiology · 2021Article
- 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
- Divergent CleLife · 2020Article
- Extracellular pH and intracellular phosphatidylinositol 4,5-bisphosphate control ClAmerican journal of physiology. Cell physiology · 2019Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- Two Cl Ions and a Glu Compete for a Helix Cage in the CLC Proton/ClBiophysical journal · 2017Article
- Probing the conformation of a conserved glutamic acid within the ClThe Journal of general physiology · 2017Article
- A pure chloride channel mutant of CLC-5 causes Dent's disease via insufficient V-ATPase activation.Pflugers Archiv : European journal of physiology · 2016Article
- 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
- Multiple discrete transitions underlie voltage-dependent activation in CLC Cl(-)/H(+) antiporters.Biophysical journal · 2014Article
- Prerequisites to proton transport in the bacterial ClC-ec1 Cl-/H+ exchanger.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
ClC-5 is a Cl(-)/H(+) antiporter that functions in endosomes and is important for endocytosis in the proximal tubule. The mechanism of transport coupling and voltage dependence in ClC-5 is unclear. Recently, a transport-deficient ClC-5 mutant (E268A) was shown to exhibit transient capacitive currents. Here, we studied the external and internal Cl(-) and pH dependence of the currents of E268A. Transient currents were almost completely independent of the intracellular pH. Even though the transient currents are modulated by extracellular pH, we could exclude that they are generated by proton-binding/unbinding reactions. In contrast, the charge movement showed a nontrivial dependence on external chloride, strongly supporting a model in which the movement of an intrinsic gating charge is followed by the voltage-dependent low-affinity binding of extracellular chloride ions. Mutation of the external Glu-211 (a residue implicated in the coupling of Cl(-) and proton transport) to aspartate abolished steady-state transport, but revealed transient currents that were shifted by ~150 mV to negative voltages compared to E268A. This identifies Glu(ext) as a major component of the gating charge underlying the transient currents of the electrogenic ClC-5 transporter. The molecular events underlying the transient currents of ClC-5 emerging from these results can be explained by an inward movement of the side chain of Glu(ext), followed by the binding of extracellular Cl(-) ions.
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Registered trials
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.