ArticleInvestigative ophthalmology & visual science2009
A mutant connexin50 with enhanced hemichannel function leads to cell death.
Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022Review
- Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract.Frontiers in cell and developmental biology · 2022Article
- Beyond the Channels: Adhesion Functions of Aquaporin 0 and Connexin 50 in Lens Development.Frontiers in cell and developmental biology · 2022Review
- Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant.Biophysical journal · 2021Article
- Article
- GJA8 missense mutation disrupts hemichannels and induces cell apoptosis in human lens epithelial cells.Scientific reports · 2019Article
- Contribution of Connexin Hemichannels to the Decreases in Cell Viability Induced by Linoleic Acid in the Human Lens Epithelial Cells (HLE-B3).Frontiers in physiology · 2019Article
- CHOP is dispensable for lens transparency in wild-type and connexin50 mutant mice.Molecular vision · 2019Article
- Chemical chaperone treatment improves levels and distributions of connexins in Cx50D47A mouse lenses.Experimental eye research · 2018Article
- Functional Characterization of Novel Atrial Fibrillation-Linked GJA5 (Cx40) Mutants.International journal of molecular sciences · 2018Article
- Article
- Physiological and Optical Alterations Precede the Appearance of Cataracts in Cx46fs380 Mice.Investigative ophthalmology & visual science · 2017Article
- Next-generation sequencing for D47N mutation in Cx50 analysis associated with autosomal dominant congenital cataract in a six-generation Chinese family.BMC ophthalmology · 2017Article
- Mutation analysis of connexin 50 gene among Iranian families with autosomal dominant cataracts.Iranian journal of basic medical sciences · 2017Article
- Focus on lens connexins.BMC cell biology · 2017Review
- The Cataract-linked Mutant Connexin50D47A Causes Endoplasmic Reticulum Stress in Mouse Lenses.The Journal of biological chemistry · 2016Article
- Further evidence for P59L mutation in GJA3 associated with autosomal dominant congenital cataract.Indian journal of ophthalmology · 2016Article
- Identification and functional analysis of two novel connexin 50 mutations associated with autosome dominant congenital cataracts.Scientific reports · 2016Article
- Connexinopathies: a structural and functional glimpse.BMC cell biology · 2016Review
- Sporadic and Familial Congenital Cataracts: Mutational Spectrum and New Diagnoses Using Next-Generation Sequencing.Human mutation · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeTo determine the consequences of expression of a novel connexin50 (CX50) mutant identified in a child with congenital total cataracts.
methodsThe GJA8 gene was directly sequenced. Formation of functional channels was assessed by the two-microelectrode voltage-clamp
methodConnexin protein levels and distribution were assessed by immunoblot analysis and immunofluorescence. The proportion of apoptotic cells was determined by flow cytometry.
resultsDirect sequencing of the GJA8 gene identified a 137 G>T transition that resulted in the replacement of glycine by valine at position 46 of the coding region of CX50 (CX50G46V). Both CX50 and CX50G46V induced gap junctional currents in pairs of Xenopus oocytes. In single Xenopus oocytes, CX50G46V induced connexin hemichannel currents that were activated by removal of external calcium; their magnitudes were much higher than those in oocytes injected with similar amounts of CX50 cRNA. When expressed in HeLa cells under the control of an inducible promoter, both CX50 and CX50G46V formed gap junctional plaques. Induction of CX50G46V expression led to a decrease in the number of cells and an increase in the proportion of apoptotic cells. CX50G46V-induced cell death was prevented by high concentrations of extracellular calcium ions.
conclusionsUnlike previously characterized CX50 mutants that exhibit impaired trafficking and/or lack of function, CX50G46V traffics properly to the plasma membrane and forms functional hemichannels and gap junction channels; however, it causes cell death even when expressed at minute levels. The biochemical results indirectly suggest a potential novel mechanism by which connexin mutants could lead to cataracts: cytotoxicity due to enhanced hemichannel function.
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