ArticleThe Journal of physiology2013
A single point mutation reveals gating of the human ClC-5 Cl-/H+ antiporter.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Biophysical Aspects of Neurodegenerative and Neurodevelopmental Disorders Involving Endo-/Lysosomal CLC ClLife (Basel, Switzerland) · 2023Review
- Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition.Molecular psychiatry · 2023Article
- 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
- Properties of single-channel and whole cell ClAmerican journal of physiology. Cell physiology · 2019Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- Helix O modulates voltage dependency of CLC-1.Pflugers Archiv : European journal of physiology · 2017Article
- A tale of two CLCs: biophysical insights toward understanding ClC-5 and ClC-7 function in endosomes and lysosomes.The Journal of physiology · 2015Review
- Salt, chloride, bleach, and innate host defense.Journal of leukocyte biology · 2015Review
- Mutations associated with Dent's disease affect gating and voltage dependence of the human anion/proton exchanger ClC-5.Frontiers in physiology · 2015Article
- F-/Cl- selectivity in CLCF-type F-/H+ antiporters.The Journal of general physiology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
ClC-5 is a 2Cl(-)/1H(+) antiporter highly expressed in endosomes of proximal tubule cells. It is essential for endocytosis and mutations in ClC-5 cause Dent's disease, potentially leading to renal failure. However, the physiological role of ClC-5 is still unclear. One of the main issues is whether the strong rectification of ClC-5 currents observed in heterologous systems, with currents elicited only at positive voltages, is preserved in vivo and what is the origin of this rectification. In this work we identified a ClC-5 mutation, D76H, which, besides the typical outward currents of the wild-type (WT), shows inward tail currents at negative potentials that allow the estimation of the reversal of ClC-5 currents for the first time. A detailed analysis of the dependence of these inward tail currents on internal and external pH and [Cl(-)] shows that they are generated by a coupled transport of Cl(-) and H(+) with a 2 : 1 stoichiometry. From this result we conclude that the inward tail currents are caused by a gating mechanism that regulates ClC-5 transport activity and not by a major alteration of the transport mechanism itself. This implies that the strong rectification of the currents of WT ClC-5 is at least in part caused by a gating mechanism that activates the transporter at positive potentials. These results elucidate the biophysical properties of ClC-5 and contribute to the understanding of its physiological role.
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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.