ArticlePloS one2012
Pathogenic connexin-31 forms constitutively active hemichannels to promote necrotic cell death.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- High Activity of Hemichannels Permeable to Calcium Ions Leads to ROS Generation and Reduced Cell Viability.International journal of molecular sciences · 2026Article
- The genetic and molecular basis of a connexin-linked skin disease.The Biochemical journal · 2024Review
- CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- 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
- Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation.International journal of molecular sciences · 2022Article
- Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels.International journal of molecular sciences · 2022Article
- Interrogation of Carboxy-Terminus LocalizedInternational journal of molecular sciences · 2022Article
- A Connexin Gene (Frontiers in genetics · 2022Article
- Erythrokeratoderma variabilis (EKV) - First Nepalese case documentingSkin health and disease · 2021Article
- Mechanisms Underlying Connexin Hemichannel Activation in Disease.International journal of molecular sciences · 2021Review
- The Complex and Critical Role of Glycine 12 (G12) in Beta-Connexins of Human Skin.International journal of molecular sciences · 2021Review
- Blockade of Hemichannels Normalizes the Differentiation Fate of Myoblasts and Features of Skeletal Muscles from Dysferlin-Deficient Mice.International journal of molecular sciences · 2020Article
- Connexin 50-R205G Mutation Perturbs Lens Epithelial Cell Proliferation and Differentiation.Investigative ophthalmology & visual science · 2020Article
- Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease.International journal of molecular sciences · 2019Review
- Connexin43 mutations linked to skin disease have augmented hemichannel activity.Scientific reports · 2019Article
- A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function.Frontiers in physiology · 2019Article
- Connexins and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- Human diseases associated with connexin mutations.Biochimica et biophysica acta. Biomembranes · 2018Review
- Cancer Connectors: Connexins, Gap Junctions, and Communication.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in Connexin-31 (Cx31) are associated with multiple human diseases including erythrokeratodermia variabilis (EKV). The molecular action of Cx31 pathogenic mutants remains largely elusive. We report here that expression of EKV pathogenic mutant Cx31R42P induces cell death with necrotic characteristics. Inhibition of hemichannel activity by a connexin hemichannel inhibitor or high extracellular calcium suppresses Cx31R42P-induced cell death. Expression of Cx31R42P induces ER stress resulting in reactive oxygen species (ROS) production, in turn, to regulate gating of Cx31R42P hemichannels and Cx31R42P induced cell death. Moreover, Cx31R42P hemichannels play an important role in mediating ATP release from the cell. In contrast, no hemichannel activity was detected with cells expressing wildtype Cx31. Together, the results suggest that Cx31R42P forms constitutively active hemichannels to promote necrotic cell death. The Cx31R42P active hemichannels are likely resulted by an ER stress mediated ROS overproduction. The study identifies a mechanism of EKV pathogenesis induced by a Cx31 mutant and provides a new avenue for potential treatment strategy of the disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.