ArticlePloS one2013
Cataract-causing mutation of human connexin 46 impairs gap junction, but increases hemichannel function and cell death.
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 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- The Mammalian Ocular Lens in Focus: Development, Anatomy, Physiology, Transparency, Biomechanics, and Age-related Challenges.Journal of visualized experiments : JoVE · 2026Review
- High Activity of Hemichannels Permeable to Calcium Ions Leads to ROS Generation and Reduced Cell Viability.International journal of molecular sciences · 2026Article
- A novel GJA3 mutation causing autosomal dominant congenital perinuclear cataracts.BMC ophthalmology · 2025Article
- CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Connexin channels and hemichannels are modulated differently by charge reversal at residues forming the intracellular pocket.Biological research · 2024Article
- Gap Junctions or Hemichannel-Dependent and Independent Roles of Connexins in Fibrosis, Epithelial-Mesenchymal Transitions, and Wound Healing.Biomolecules · 2023Review
- Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- Gap Junction Channelopathies and Calmodulinopathies. Do Disease-Causing Calmodulin Mutants Affect Direct Cell-Cell Communication?International journal of molecular sciences · 2021Review
- Article
- Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish.Communications biology · 2021Article
- Regulation of Connexin Gap Junctions and Hemichannels by Calcium and Calcium Binding Protein Calmodulin.International journal of molecular sciences · 2020Review
- Calmodulin-Mediated Regulation of Gap Junction Channels.International journal of molecular sciences · 2020Review
- GJA8 missense mutation disrupts hemichannels and induces cell apoptosis in human lens epithelial cells.Scientific reports · 2019Article
- A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function.Frontiers in physiology · 2019Article
- Article
- Cataract-associated connexin 46 mutation alters its interaction with calmodulin and function of hemichannels.The Journal of biological chemistry · 2018Article
- Monocytic cell junction proteins serve important roles in atherosclerosis via the endoglin pathway.Molecular medicine reports · 2017Article
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Biological responses of osteocytic connexin 43 hemichannels to simulated microgravity.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Connexin channels play a critical role in maintaining metabolic homeostasis and transparency of the lens. Mutations in connexin genes are linked to congenital cataracts in humans. The G143R missense mutation on connexin (Cx) 46 was recently reported to be associated with congenital Coppock cataracts. Here, we showed that the G143R mutation decreased Cx46 gap junctional coupling in a dominant negative manner; however, it significantly increased gap junctional plaques. The G143R mutant also increased hemichannel activity, inversely correlated with the level of Cx46 protein on the cell surface. The interaction between cytoplasmic loop domain and C-terminus has been shown to be involved in gating of connexin channels. Interestingly, the G143R mutation enhanced the interaction between intracellular loop and Cx46. Furthermore, this mutation decreased cell viability and the resistance of the cells to oxidative stress, primarily due to the increased hemichannel function. Together, these results suggest that mutation of this highly conserved residue on the cytoplasmic loop domain of Cx46 enhances its interaction with the C-terminus, resulting in a reduction of gap junction channel function, but increased hemichannel function. This combination leads to the development of human congenital cataracts.
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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.