ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Photoactivation-induced instability of rhodopsin mutants T4K and T17M in rod outer segments underlies retinal degeneration in X. laevis transgenic models of retinitis pigmentosa.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 37 citations in OpenAlex.
- Glycosylation of the retina.Biochemical Society transactions · 2026Review
- A Survey of Opsin Localization, Glycosylation, and Light/Chromophore Influence on Degeneration in 26 Rhodopsin-Associated RP Models.Investigative ophthalmology & visual science · 2025Article
- Systematic review:Frontiers in medicine · 2025Review
- Synchronized Photoactivation of T4K Rhodopsin Causes a Chromophore-Dependent Retinal Degeneration That Is Moderated by Interaction with Phototransduction Cascade Components.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Understanding the Rhodopsin Worldview Through Atomic Force Microscopy (AFM): Structure, Stability, and Activity Studies.Chemical record (New York, N.Y.) · 2023Review
- The role of motor proteins in photoreceptor protein transport and visual function.Ophthalmic genetics · 2022Article
- Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.JCI insight · 2022Article
- Sector Retinitis Pigmentosa: Extending the Molecular Genetics Basis and Elucidating the Natural History.American journal of ophthalmology · 2021Article
- SRD005825 Acts as a Pharmacologic Chaperone of Opsin and Promotes Survival of Photoreceptors in an Animal Model of Autosomal Dominant Retinitis Pigmentosa.Translational vision science & technology · 2019Article
- Autophagy inAutophagy · 2019Article
- HeterozygousBioscience reports · 2019Article
- Sector retinitis pigmentosa: Report of ten cases and a review of the literature.Molecular vision · 2019Review
- Targeted disruption of the endogenous zebrafishMolecular vision · 2018Article
- The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy.Progress in retinal and eye research · 2018Review
- Modeling Dominant and Recessive Forms of Retinitis Pigmentosa by Editing Three Rhodopsin-Encoding Genes in Xenopus Laevis Using Crispr/Cas9.Scientific reports · 2017Article
- Valproic Acid for a Treatment of Retinitis Pigmentosa: Reasons for Optimism and Caution.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Opposing Effects of Valproic Acid Treatment Mediated by Histone Deacetylase Inhibitor Activity in Four TransgenicThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Retinal Degeneration and Regeneration-Lessons From Fishes and Amphibians.Current pathobiology reports · 2017Review
- Acute and Protracted Cell Death in Light-Induced Retinal Degeneration in the Canine Model of Rhodopsin Autosomal Dominant Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2017Article
- Structural and molecular bases of rod photoreceptor morphogenesis and disease.Progress in retinal and eye research · 2016Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Retinitis pigmentosa (RP) is an inherited neurodegenerative disease involving progressive vision loss, and is often linked to mutations in the rhodopsin gene. Mutations that abolish N-terminal glycosylation of rhodopsin (T4K and T17M) cause sector RP in which the inferior retina preferentially degenerates, possibly due to greater light exposure of this region. Transgenic animal models expressing rhodopsin glycosylation mutants also exhibit light exacerbated retinal degeneration (RD). In this study, we used transgenic Xenopus laevis to investigate the pathogenic mechanism connecting light exposure and RD in photoreceptors expressing T4K or T17M rhodopsin. We demonstrate that increasing the thermal stability of these rhodopsins via a novel disulfide bond resulted in significantly less RD. Furthermore, T4K or T17M rhodopsins that were constitutively inactive (due to lack of the chromophore-binding site or dietary deprivation of the chromophore precursor vitamin A) induced less toxicity. In contrast, variants in the active conformation accumulated in the ER and caused RD even in the absence of light. In vitro, T4K and T17M rhodopsins showed reduced ability to regenerate pigment after light exposure. Finally, although multiple amino acid substitutions of T4 abolished glycosylation at N2 but were not toxic, similar substitutions of T17 were not tolerated, suggesting that the carbohydrate moiety at N15 is critical for cell viability. Our results identify a novel pathogenic mechanism in which the glycosylation-deficient rhodopsins are destabilized by light activation. These results have important implications for proposed RP therapies, such as vitamin A supplementation, which may be ineffective or even detrimental for certain RP genotypes.
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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.