ArticleInvestigative ophthalmology & visual science2016
Identification and Functional Assessment of Age-Dependent Truncations to Cx46 and Cx50 in the Human Lens.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Effect of hydrogen peroxide on lens transparency, intracellular pH, gap junction coupling, hydrostatic pressure and membrane water permeability.Experimental eye research · 2024Article
- Dual diagnosis ofRare (Amsterdam, Netherlands) · 2024Article
- The Role of Gap Junctions Dysfunction in the Development of Cataracts: From Loss of Cell-to-Cell Transfer to Blurred Vision-Review.Bioelectricity · 2023Review
- KI04 an Aminoglycosides-Derived Molecule Acts as an Inhibitor of Human Connexin46 Hemichannels Expressed in HeLa Cells.Biomolecules · 2023Article
- Mutations of CX46/CX50 and Cataract Development.Frontiers in molecular biosciences · 2022Review
- Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens.Frontiers in physiology · 2022Review
- Beyond the Channels: Adhesion Functions of Aquaporin 0 and Connexin 50 in Lens Development.Frontiers in cell and developmental biology · 2022Review
- Lens Aquaporins in Health and Disease: Location is Everything!Frontiers in physiology · 2022Review
- Loss of fiber cell communication may contribute to the development of cataracts of many different etiologies.Frontiers in physiology · 2022Review
- Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells.International journal of molecular sciences · 2021Article
- Article
- Proteomic characterization of the human lens and Cataractogenesis.Expert review of proteomics · 2021Review
- Physiological Mechanisms Regulating Lens Transport.Frontiers in physiology · 2021Review
- Spatiotemporal changes in the human lens proteome: Critical insights into long-lived proteins.Progress in retinal and eye research · 2020Review
- Cleavage C-terminal to Asp leads to covalent crosslinking of long-lived human proteins.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- Concatenation of Human Connexin26 (hCx26) and Human Connexin46 (hCx46) for the Analysis of Heteromeric Gap Junction Hemichannels and Heterotypic Gap Junction Channels.International journal of molecular sciences · 2018Article
- Connexin32 plays a crucial role in ROS-mediated endoplasmic reticulum stress apoptosis signaling pathway in ischemia reperfusion-induced acute kidney injury.Journal of translational medicine · 2018Article
- Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins.Investigative ophthalmology & visual science · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
purposeMany proteins in the lens undergo extensive posttranslational modifications (PTMs) with age, leading to alterations in their function. The extent to which lens gap junction proteins, Cx46 and Cx50, accumulate PTMs with aging is not known. In this study, we identified truncations in Cx46 and Cx50 in the human lens using mass spectrometry. We also examined the effect of truncations on channel function using electrophysiological measurements.
methodsHuman lenses were dissected into cortex, outer nucleus, and nucleus regions, and fiber cell membranes were subjected to trypsin digestion. Tryptic peptides were analyzed by liquid chromatography (LC)-electrospray tandem mass spectrometry (ESI/MS/MS). Effects of truncations on channel conductance, permeability, and gating were assessed in transfected cells.
resultsCleavage sites were identified in the C-terminus, the cytoplasmic loop, and the N-terminus of Cx46 and Cx50. Levels of C-terminal truncations, which were found at residues 238 to 251 in Cx46 and at residues 238 to 253 and 274 to 284 in Cx50, were similar in different lens regions. In contrast, levels of truncations in cytoplasmic loop and N-terminal domains of Cx46 and Cx50 increased dramatically from outer cortex to nucleus. Most of the C-terminally truncated proteins were functional, whereas truncations in the cytoplasmic loop did not result in the formation of functional channels.
conclusionsAccumulation of cytoplasmic loop and N-terminal truncations in the core might lead to decreases in coupling with age. This reduction is expected to lead to an increase in intracellular calcium and a decrease in levels of glutathione in the nucleus. These changes may ultimately lead to age-related nuclear cataracts.
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