ArticleThe Biochemical journal2012
Defective trafficking of cone photoreceptor CNG channels induces the unfolded protein response and ER-stress-associated cell death.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine.Biomolecules · 2025Review
- A review of the 661W cell line as a tool to facilitate treatment development for retinal diseases.Cell & bioscience · 2025Review
- Unlocking cellular traffic jams: olive oil-mediated rescue of CNG mutant channels.Frontiers in pharmacology · 2024Article
- Review
- 4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene.Journal of thoracic disease · 2023Article
- Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.Biomedicines · 2023Review
- Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision.Journal of translational medicine · 2022Review
- Evaluation of photoreceptor-directed fibroblasts derived from retinitis pigmentosa patients with defects in the EYS gene: a possible cost-effective cellular model for mechanism-oriented drug.Stem cell research & therapy · 2022Article
- Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel.Communications biology · 2022Article
- Achromatopsia: Genetics and Gene Therapy.Molecular diagnosis & therapy · 2022Review
- Mitigating the pro-oxidant state and melanogenesis of Retinitis pigmentosa: by counteracting mitochondrial dysfunction.Cellular and molecular life sciences : CMLS · 2021Review
- 2,3,5,6-Tetramethylpyrazine protects retinal photoreceptors against endoplasmic reticulum stress by modulating ATF4-mediated inhibition of PRP aggregation.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa.Scientific reports · 2020Article
- Tauroursodeoxycholic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Injury and Endoplasmic Reticulum Stress In Vitro.Biomedicines · 2020Article
- Assistance for Folding of Disease-Causing Plasma Membrane Proteins.Biomolecules · 2020Review
- Melatonin receptor heterodimerization in a photoreceptor-like cell line endogenously expressing melatonin receptors.Molecular vision · 2019Article
- Neuroprotective strategies for retinal disease.Progress in retinal and eye research · 2018Review
- Melatonin partially protects 661W cells from HMolecular vision · 2017Article
- Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.Molecules (Basel, Switzerland) · 2015Review
- Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels.Frontiers in physiology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations that perturb the function of photoreceptor CNG (cyclic nucleotide-gated) channels are associated with several human retinal disorders, but the molecular and cellular mechanisms leading to photoreceptor dysfunction and degeneration remain unclear. Many loss-of-function mutations result in intracellular accumulation of CNG channel subunits. Accumulation of proteins in the ER (endoplasmic reticulum) is known to cause ER stress and trigger the UPR (unfolded protein response), an evolutionarily conserved cellular programme that results in either adaptation via increased protein processing capacity or apoptotic cell death. We hypothesize that defective trafficking of cone photoreceptor CNG channels can induce UPR-mediated cell death. To test this idea, CNGA3 subunits bearing the R563H and Q655X mutations were expressed in photoreceptor-derived 661W cells with CNGB3 subunits. Compared with wild-type, R563H and Q655X subunits displayed altered degradation rates and/or were retained in the ER. ER retention was associated with increased expression of UPR-related markers of ER stress and with decreased cell viability. Chemical and pharmacological chaperones {TUDCA (tauroursodeoxycholate sodium salt), 4-PBA (sodium 4-phenylbutyrate) and the cGMP analogue CPT-cGMP [8-(4-chlorophenylthio)-cGMP]} differentially reduced degradation and/or promoted plasma-membrane localization of defective subunits. Improved subunit maturation was concordant with reduced expression of ER-stress markers and improved viability of cells expressing localization-defective channels. These results indicate that ER stress can arise from expression of localization-defective CNG channels, and may represent a contributing factor for photoreceptor degeneration.
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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.