ArticleThe Journal of biological chemistry2014
Inherent instability of the retinitis pigmentosa P23H mutant opsin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- Disease mechanisms revealed in the P23H opsin knock-in mouse model of retinitis pigmentosa.PNAS nexus · 2026Article
- 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
- Compensation of inner retina to early-stage photoreceptor degeneration in a RhoExperimental eye research · 2024Article
- Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.Nature communications · 2023Article
- Primary versus Secondary Elevations in Fundus Autofluorescence.International journal of molecular sciences · 2023Review
- Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23HGene therapy · 2023Article
- Sigma 1 receptor activation improves retinal structure and function in the RhoExperimental eye research · 2023Article
- Chromenone derivatives as novel pharmacological chaperones for retinitis pigmentosa-linked rod opsin mutants.Human molecular genetics · 2022Article
- Lysosome docking to WIPI1 rings and ER-connected phagophores occurs during DNAJB12- and GABARAP-dependent selective autophagy of misfolded P23H-rhodopsin.Molecular biology of the cell · 2022Article
- Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.JCI insight · 2022Article
- Flavonoids improve the stability and function of P23H rhodopsin slowing down the progression of retinitis pigmentosa in mice.Journal of neuroscience research · 2022Article
- Rhodopsin as a Molecular Target to Mitigate Retinitis Pigmentosa.Advances in experimental medicine and biology · 2022Review
- Modulation of SOD3 Levels Is Detrimental to Retinal Homeostasis.Antioxidants (Basel, Switzerland) · 2021Article
- Structural aspects of rod opsin and their implication in genetic diseases.Pflugers Archiv : European journal of physiology · 2021Review
- Article
- AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity.Human molecular genetics · 2020Article
- Conformational perturbation, allosteric modulation of cellular signaling pathways, and disease in P23H rhodopsin.Scientific reports · 2020Article
- Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation.Molecular neurobiology · 2020Article
- Screening of Chemical Libraries Using a Yeast Model of Retinal Disease.SLAS discovery : advancing life sciences R & D · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The P23H opsin mutation is the most common cause of autosomal dominant retinitis pigmentosa. Even though the pathobiology of the resulting retinal degeneration has been characterized in several animal models, its complex molecular mechanism is not well understood. Here, we expressed P23H bovine rod opsin in the nervous system of Caenorhabditis elegans. Expression was low due to enhanced protein degradation. The mutant opsin was glycosylated, but the polysaccharide size differed from that of the normal protein. Although P23H opsin aggregated in the nervous system of C. elegans, the pharmacological chaperone 9-cis-retinal stabilized it during biogenesis, producing a variant of rhodopsin called P23H isorhodopsin. In vitro, P23H isorhodopsin folded correctly, formed the appropriate disulfide bond, could be photoactivated but with reduced sensitivity, and underwent Meta II decay at a rate similar to wild type isorhodopsin. In worm neurons, P23H isorhodopsin initiated phototransduction by coupling with the endogenous Gi/o signaling cascade that induced loss of locomotion. Using pharmacological interventions affecting protein synthesis and degradation, we showed that the chromophore could be incorporated either during or after mutant protein translation. However, regeneration of P23H isorhodopsin with chromophore was significantly slower than that of wild type isorhodopsin. This effect, combined with the inherent instability of P23H rhodopsin, could lead to the structural cellular changes and photoreceptor death found in autosomal dominant retinitis pigmentosa. These results also suggest that slow regeneration of P23H rhodopsin could prevent endogenous chromophore-mediated stabilization of rhodopsin in the retina.
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