ArticleThe Journal of biological chemistry2013
Common gating of both CLC transporter subunits underlies voltage-dependent activation of the 2Cl-/1H+ exchanger ClC-7/Ostm1.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Abnormal ClC-3/TMEM9-mediated endosomal ion transport in CLCN3-associated neurodevelopmental disease.EMBO molecular medicine · 2026Article
- Osteopetrosis: Pathogenesis, Clinical Management, and Emerging Therapies.Current osteoporosis reports · 2026Review
- Dominant Action ofCells · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Role of voltage-gated chloride channels in epilepsy: current insights and future directions.Frontiers in pharmacology · 2025Review
- Review
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023Article
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution.The Journal of cell biology · 2023Article
- 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
- Article
- The Role of the Lysosomal ClCells · 2022Review
- 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
- Neurodegeneration Upon Dysfunction of Endosomal/Lysosomal CLC Chloride Transporters.Frontiers in cell and developmental biology · 2021Review
- A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 ClAmerican journal of human genetics · 2020Article
- Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.eLife · 2020Article
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5 authors.
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Abstract
CLC anion transporters form dimers that function either as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers. CLC channels display two different types of "gates," "protopore" gates that open and close the two pores of a CLC dimer independently of each other and common gates that act on both pores simultaneously. ClC-7/Ostm1 is a lysosomal 2Cl(-)/1H(+) exchanger that is slowly activated by depolarization. This gating process is drastically accelerated by many CLCN7 mutations underlying human osteopetrosis. Making use of some of these mutants, we now investigate whether slow voltage activation of plasma membrane-targeted ClC-7/Ostm1 involves protopore or common gates. Voltage activation of wild-type ClC-7 subunits was accelerated by co-expressing an excess of ClC-7 subunits carrying an accelerating mutation together with a point mutation rendering these subunits transport-deficient. Conversely, voltage activation of a fast ClC-7 mutant could be slowed by co-expressing an excess of a transport-deficient mutant. These effects did not depend on whether the accelerating mutation localized to the transmembrane part or to cytoplasmic cystathionine-β-synthase (CBS) domains of ClC-7. Combining accelerating mutations in the same subunit did not speed up gating further. No currents were observed when ClC-7 was truncated after the last intramembrane helix. Currents and slow gating were restored when the C terminus was co-expressed by itself or fused to the C terminus of the β-subunit Ostm1. We conclude that common gating underlies the slow voltage activation of ClC-7. It depends on the CBS domain-containing C terminus that does not require covalent binding to the membrane domain of ClC-7.
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