ArticleThe EMBO journal2011
ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 218 citations in OpenAlex.
- Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026Review
- Folding and Oligomerization of CLC Channels and Transporters.Chemical reviews · 2026Review
- The molecular and functional interplay between the osteopetrosis-associated proteins SNX10, OSTM1, and CLC-7 during mouse osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Osteopetrosis: Pathogenesis, Clinical Management, and Emerging Therapies.Current osteoporosis reports · 2026Review
- Circadian regulation of osteoclast lysosomal-resorption machinery: implications for osteoporosis therapy.Frontiers in cell and developmental biology · 2026Review
- A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)PNature structural & molecular biology · 2025Article
- Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.The Journal of cell biology · 2025Article
- Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson's disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation.NPJ Parkinson's disease · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Delayed vacuolation in mammalian cells caused by hypotonicity and ion loss.Scientific reports · 2024Article
- Molecular Heterogeneity of Osteopetrosis in India: Report of 17 Novel Variants.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2024Article
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction.Calcified tissue international · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal ClBiomolecules · 2023Article
- 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
66 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the ClC-7/Ostm1 ion transporter lead to osteopetrosis and lysosomal storage disease. Its lysosomal localization hitherto precluded detailed functional characterization. Using a mutated ClC-7 that reaches the plasma membrane, we now show that both the aminoterminus and transmembrane span of the Ostm1 β-subunit are required for ClC-7 Cl(-)/H(+)-exchange, whereas the Ostm1 transmembrane domain suffices for its ClC-7-dependent trafficking to lysosomes. ClC-7/Ostm1 currents were strongly outwardly rectifying owing to slow gating of ion exchange, which itself displays an intrinsically almost linear voltage dependence. Reversal potentials of tail currents revealed a 2Cl(-)/1H(+)-exchange stoichiometry. Several disease-causing CLCN7 mutations accelerated gating. Such mutations cluster to the second cytosolic cystathionine-β-synthase domain and potential contact sites at the transmembrane segment. Our work suggests that gating underlies the rectification of all endosomal/lysosomal CLCs and extends the concept of voltage gating beyond channels to ion exchangers.
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