ArticleScientific reports2016
Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Restoration of Shal/KCellular and molecular life sciences : CMLS · 2025Article
- Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance.Biomolecules · 2022Review
- Chaperone activity of niflumic acid on ClC-1 chloride channel mutants causing myotonia congenita.Frontiers in pharmacology · 2022Article
- Regulation of ClC-2 Chloride Channel Proteostasis by Molecular Chaperones: Correction of Leukodystrophy-Associated Defect.International journal of molecular sciences · 2021Article
- Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions.Cell stress & chaperones · 2021Review
- Skeletal muscle ClC-1 chloride channels in health and diseases.Pflugers Archiv : European journal of physiology · 2020Review
- Pathomechanisms of aFrontiers in neurology · 2020Article
- Changes in Expression and Cellular Localization of Rat Skeletal Muscle ClC-1 Chloride Channel in Relation to Age, Myofiber Phenotype and PKC Modulation.Frontiers in pharmacology · 2020Article
- Defective Gating and Proteostasis of Human ClC-1 Chloride Channel: Molecular Pathophysiology of Myotonia Congenita.Frontiers in neurology · 2020Review
- Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid receptor-mediated changes in colon epithelial tight junction proteins, barrier function, and visceral pain in the rodent and human.Neurogastroenterology and motility · 2019Article
- FKBP8 Enhances Protein Stability of the CLC-1 Chloride Channel at the Plasma Membrane.International journal of molecular sciences · 2018Article
- Unfolding of a ClC chloride transporter retains memory of its evolutionary history.Nature chemical biology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation.
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Registered trials
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