ArticleScientific reports2019
Connexin43 mutations linked to skin disease have augmented hemichannel activity.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 49 citations in OpenAlex.
- COeLife · 2026Article
- The genetic and molecular basis of a connexin-linked skin disease.The Biochemical journal · 2024Review
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions.Frontiers in physiology · 2024Review
- Increased Hemichannel Activity Displayed by a Connexin43 Mutation Causing a Familial Connexinopathy Exhibiting Hypotrichosis with Follicular Keratosis and Hyperostosis.International journal of molecular sciences · 2023Article
- Article
- Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes: The Importance of Functional Studies above Prediction.International journal of molecular sciences · 2022Review
- Cellular mechanisms of connexin-based inherited diseases.Trends in cell biology · 2022Review
- Interrogation of Carboxy-Terminus LocalizedInternational journal of molecular sciences · 2022Article
- Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome.Scientific reports · 2021Article
- Connexin Genes Variants Associated with Non-Syndromic Hearing Impairment: A Systematic Review of the Global Burden.Life (Basel, Switzerland) · 2020Review
- Comparative Analysis of Cx31 and Cx43 in Differentiation-Competent Rodent Keratinocytes.Biomolecules · 2020Article
- Signaling Between TRPV1/TRPV4 and Intracellular Hydrostatic Pressure in the Mouse Lens.Investigative ophthalmology & visual science · 2020Article
- S-nitrosylation of connexin43 hemichannels elicits cardiac stress-induced arrhythmias in Duchenne muscular dystrophy mice.JCI insight · 2019Article
- Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease.International journal of molecular sciences · 2019Review
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the gene (GJA1) encoding connexin43 (Cx43) are responsible for several rare genetic disorders, including non-syndromic skin-limited diseases. Here we used two different functional expression systems to characterize three Cx43 mutations linked to palmoplantar keratoderma and congenital alopecia-1, erythrokeratodermia variabilis et progressiva, or inflammatory linear verrucous epidermal nevus. In HeLa cells and Xenopus oocytes, we show that Cx43-G8V, Cx43-A44V and Cx43-E227D all formed functional gap junction channels with the same efficiency as wild-type Cx43, with normal voltage gating and a unitary conductance of ~110 pS. In HeLa cells, all three mutations also localized to regions of cell-cell contact and displayed a punctate staining pattern. In addition, we show that Cx43-G8V, Cx43-A44V and Cx43-E227D significantly increase membrane current flow through formation of active hemichannels, a novel activity that was not displayed by wild-type Cx43. The increased membrane current was inhibited by either 2 mM calcium, or 5 µM gadolinium, mediated by hemichannels with a unitary conductance of ~250 pS, and was not due to elevated mutant protein expression. The three Cx43 mutations all showed the same gain of function activity, suggesting that augmented hemichannel activity could play a role in skin-limited diseases caused by human Cx43 mutations.
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