ArticlePloS one2013
Myotonia congenita mutation enhances the degradation of human CLC-1 chloride channels.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular mechanism of hyperactivation conferred by a truncation of TRPA1.Nature communications · 2023Article
- Chaperone activity of niflumic acid on ClC-1 chloride channel mutants causing myotonia congenita.Frontiers in pharmacology · 2022Article
- First Two Case Reports of Becker's Type Myotonia Congenita in Colombia: Clinical and Genetic Features.The application of clinical genetics · 2021Article
- Skeletal muscle ClC-1 chloride channels in health and diseases.Pflugers Archiv : European journal of physiology · 2020Review
- Functional Study of Novel Bartter's Syndrome Mutations in ClC-Kb and Rescue by the Accessory Subunit Barttin Toward Personalized Medicine.Frontiers in pharmacology · 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
- Article
- Defective Gating and Proteostasis of Human ClC-1 Chloride Channel: Molecular Pathophysiology of Myotonia Congenita.Frontiers in neurology · 2020Review
- A large intragenic deletion in the CLCN1 gene causes Hereditary Myotonia in pigs.Scientific reports · 2019Article
- FKBP8 Enhances Protein Stability of the CLC-1 Chloride Channel at the Plasma Membrane.International journal of molecular sciences · 2018Article
- Electrophysiological characteristics of R47W and A298T mutations in CLC-1 of myotonia congenita patients and evaluation of clinical features.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.Frontiers in pharmacology · 2017Review
- Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.Scientific reports · 2016Article
- Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations.Scientific reports · 2015Article
- The Cullin 4A/B-DDB1-Cereblon E3 Ubiquitin Ligase Complex Mediates the Degradation of CLC-1 Chloride Channels.Scientific reports · 2015Article
- Mutational consequences of aberrant ion channels in neurological disorders.The Journal of membrane biology · 2014Review
- Article
- CLC channel function and dysfunction in health and disease.Frontiers in physiology · 2014Review
- Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes.Experimental neurology · 2013Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
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Abstract
Myotonia congenita is a hereditary muscle disorder caused by mutations in the human voltage-gated chloride (Cl(-)) channel CLC-1. Myotonia congenita can be inherited in an autosomal recessive (Becker type) or dominant (Thomsen type) fashion. One hypothesis for myotonia congenita is that the inheritance pattern of the disease is determined by the functional consequence of the mutation on the gating of CLC-1 channels. Several disease-related mutations, however, have been shown to yield functional CLC-1 channels with no detectable gating defects. In this study, we have functionally and biochemically characterized a myotonia mutant: A531V. Despite a gating property similar to that of wild-type (WT) channels, the mutant CLC-1 channel displayed a diminished whole-cell current density and a reduction in the total protein expression level. Our biochemical analyses further demonstrated that the reduced expression of A531V can be largely attributed to an enhanced proteasomal degradation as well as a defect in protein trafficking to surface membranes. Moreover, the A531V mutant protein also appeared to be associated with excessive endosomal-lysosomal degradation. Neither the reduced protein expression nor the diminished current density was rescued by incubating A531V-expressing cells at 27°C. These results demonstrate that the molecular pathophysiology of A531V does not involve anomalous channel gating, but rather a disruption of the balance between the synthesis and degradation of the CLC-1 channel protein.
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