ArticlePLoS genetics2010
Inactivation of VCP/ter94 suppresses retinal pathology caused by misfolded rhodopsin in Drosophila.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
- Advances in Research on Endoplasmic Reticulum-Associated Degradation Mechanisms in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
- Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study.BMC medicine · 2026Article
- Endoplasmic reticulum stress and rhodopsin accumulation in an organoid model of Retinitis Pigmentosa carrying a RHO pathogenic variant.Stem cell research & therapy · 2025Article
- Article
- Mutant dominant-negativeFrontiers in molecular biosciences · 2024Article
- PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy.The Journal of cell biology · 2023Article
- Article
- Network biology analysis of P23H rhodopsin interactome identifies protein and mRNA quality control mechanisms.Scientific reports · 2022Article
- Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.JCI insight · 2022Article
- Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOBiomolecules · 2021Article
- Drosophila fabp is required for light-dependent Rhodopsin-1 clearance and photoreceptor survival.PLoS genetics · 2021Article
- Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection.Nature communications · 2021Article
- Efficient Ocular Delivery of VCP siRNA via Reverse Magnetofection in RHO P23H Rodent Retina Explants.Pharmaceutics · 2021Article
- ER membrane protein complex is required for the insertions of late-synthesized transmembrane helices of Rh1 inMolecular biology of the cell · 2019Article
- Human eye conditions: insights from the fly eye.Human genetics · 2019Review
- Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis.Cell cycle (Georgetown, Tex.) · 2019Article
- NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene.Scientific reports · 2018Article
- The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy.Progress in retinal and eye research · 2018Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most common Rhodopsin (Rh) mutation associated with autosomal dominant retinitis pigmentosa (ADRP) in North America is the substitution of proline 23 by histidine (Rh(P23H)). Unlike the wild-type Rh, mutant Rh(P23H) exhibits folding defects and forms intracellular aggregates. The mechanisms responsible for the recognition and clearance of misfolded Rh(P23H) and their relevance to photoreceptor neuron (PN) degeneration are poorly understood. Folding-deficient membrane proteins are subjected to Endoplasmic Reticulum (ER) quality control, and we have recently shown that Rh(P23H) is a substrate of the ER-associated degradation (ERAD) effector VCP/ter94, a chaperone that extracts misfolded proteins from the ER (a process called retrotranslocation) and facilitates their proteasomal degradation. Here, we used Drosophila, in which Rh1(P37H) (the equivalent of mammalian Rh(P23H)) is expressed in PNs, and found that the endogenous Rh1 is required for Rh1(P37H) toxicity. Genetic inactivation of VCP increased the levels of misfolded Rh1(P37H) and further activated the Ire1/Xbp1 ER stress pathway in the Rh1(P37H) retina. Despite this, Rh1(P37H) flies with decreased VCP function displayed a potent suppression of retinal degeneration and blindness, indicating that VCP activity promotes neurodegeneration in the Rh1(P37H) retina. Pharmacological treatment of Rh1(P37H) flies with the VCP/ERAD inhibitor Eeyarestatin I or with the proteasome inhibitor MG132 also led to a strong suppression of retinal degeneration. Collectively, our findings raise the possibility that excessive retrotranslocation and/or degradation of visual pigment is a primary cause of PN degeneration.
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