ArticlePloS one2010
The G215R mutation in the Cl-/H+-antiporter ClC-7 found in ADO II osteopetrosis does not abolish function but causes a severe trafficking defect.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Preparation of Plasma Membrane Vesicles, Lysosomes, Proteoliposomes and Alternative Sample Types for SSM-Based Electrophysiology.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes.Nature communications · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Identification of a novel mutation in theFrontiers in pediatrics · 2025Article
- Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (Biomolecules · 2024Article
- Effect of Roflumilast, a Selective PDE4 Inhibitor, on Bone Phenotypes in ADO2 Mice.Calcified tissue international · 2024Article
- The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction.Calcified tissue international · 2024Article
- A Comparative Study on the Lysosomal Cation Channel TMEM175 Using Automated Whole-Cell Patch-Clamp, Lysosomal Patch-Clamp, and Solid Supported Membrane-Based Electrophysiology: Functional Characterization and High-Throughput Screening Assay Development.International journal of molecular sciences · 2023Article
- The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants.PLoS genetics · 2023Article
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- The Role of the Lysosomal ClCells · 2022Review
- Article
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Neurodegeneration Upon Dysfunction of Endosomal/Lysosomal CLC Chloride Transporters.Frontiers in cell and developmental biology · 2021Review
- Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.eLife · 2020Article
- Functional Characterization of SLC Transporters Using Solid Supported Membranes.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration.Biomolecules · 2019Review
- Article
- Enhanced Activation of Rac1/Cdc42 and MITF Leads to Augmented Osteoclastogenesis in Autosomal Dominant Osteopetrosis Type II.JBMR plus · 2019Article
- Extra-skeletal manifestations in mice affected byBone research · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClC-7 is a ubiquitous transporter which is broadly expressed in mammalian tissues. It is implied in the pathogenesis of lysosomal storage disease and osteopetrosis. Because of its endosomal/lysosomal localization it is still poorly characterized. METHODOLOGY/PRINCIPAL
findingsAn electrophysiological characterization of rat ClC-7 using solid-supported membrane-based electrophysiology is presented. The measured currents show the characteristics of ClC-7 and confirm its function as a Cl(-)/H(+)-antiporter. We have used rat ClC-7 in CHO cells as a model system to investigate the functionality and cellular localization of the wt transporter and its variant G213R ClC-7 which is the analogue of human G215R ClC-7 responsible for autosomal dominant osteopetrosis type II. Our study shows that rat G213R ClC-7 is functional but has a localization defect in CHO cells which prevents it from being correctly targeted to the lysosomal membrane. The electrophysiological assay is tested as a tool for drug discovery. The assay is validated with a number of drug candidates. It is shown that ClC-7 is inhibited by DIDS, NPPB and NS5818 at micromolar concentrations. CONCLUSIONS/SIGNIFICANCE: It is suggested that the scenario found in the CHO model system also applies to the human transporter and that mislocalization rather than impaired functionality of G215R ClC-7 is the primary cause of the related autosomal dominant osteopetrosis type II. Furthermore, the robust solid-supported membrane-based electrophysiological assay is proposed for rapid screening for potential ClC-7 inhibitors which are discussed for treatment of osteoporosis.
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