ArticleThe Journal of biological chemistry2010
The late endosomal ClC-6 mediates proton/chloride countertransport in heterologous plasma membrane expression.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Blood pressure loci identified with a gene-centric array.American journal of human genetics · 2011Pooled it
- mRAVE governs lysosomal catabolism through basal and mTORC1-regulated V-ATPase assembly.The EMBO journal · 2026Article
- Folding and Oligomerization of CLC Channels and Transporters.Chemical reviews · 2026Review
- A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025Article
- Biophysical characterization of anion channels in mitochondrion-endoplasmic-reticulum contact sites.Biophysical journal · 2025Article
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Case report: ocular manifestations of a gain-of-function mutation inOphthalmic genetics · 2024Article
- The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction.Calcified tissue international · 2024Article
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- Biophysical Aspects of Neurodegenerative and Neurodevelopmental Disorders Involving Endo-/Lysosomal CLC ClLife (Basel, Switzerland) · 2023Review
- The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants.PLoS genetics · 2023Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Vesicular CLC chloride/proton exchangers in health and diseases.Frontiers in pharmacology · 2023Review
- Modulation of blood pressure regulatory genes in the Agtrap-Plod1 locus associated with a deletion in Clcn6.Physiological reports · 2022Article
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- The Role of the Lysosomal ClCells · 2022Review
- West Syndrome Caused By a Chloride/Proton Exchange-Uncoupling CLCN6 Mutation Related to Autophagic-Lysosomal Dysfunction.Molecular neurobiology · 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
- Loss of Chloride Channel 6 (CLC-6) Affects Vascular Smooth Muscle Contractility and Arterial Stiffness via Alterations to Golgi Calcium Stores.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Reduced Graphene Oxides Modulate the Expression of Cell Receptors and Voltage-Dependent Ion Channel Genes of Glioblastoma Multiforme.International journal of molecular sciences · 2021Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Members of the CLC protein family of Cl(-) channels and transporters display the remarkable ability to function as either chloride channels or Cl(-)/H(+) antiporters. Due to the intracellular localization of ClC-6 and ClC-7, it has not yet been possible to study the biophysical properties of these members of the late endosomal/lysosomal CLC branch in heterologous expression. Whereas recent data suggest that ClC-7 functions as an antiporter, transport characteristics of ClC-6 have remained entirely unknown. Here, we report that fusing the green fluorescent protein (GFP) to the N terminus of ClC-6 increased its cell surface expression, allowing us to functionally characterize ClC-6. Compatible with ClC-6 mediating Cl(-)/H(+) exchange, Xenopus oocytes expressing GFP-tagged ClC-6 alkalinized upon depolarization. This alkalinization was dependent on the presence of extracellular anions and could occur against an electrochemical proton gradient. As observed in other CLC exchangers, ClC-6-mediated H(+) transport was abolished by mutations in either the "gating" or "proton" glutamate. Overexpression of GFP-tagged ClC-6 in CHO cells elicited small, outwardly rectifying currents with a Cl(-) > I(-) conductance sequence. Mutating the gating glutamate of ClC-6 yielded an ohmic anion conductance that was increased by additionally mutating the "anion-coordinating" tyrosine. Additionally changing the chloride-coordinating serine 157 to proline increased the NO(3)(-) conductance of this mutant. Taken together, these data demonstrate for the first time that ClC-6 is a Cl(-)/H(+) antiporter.
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