ArticleScientific reports2019
The dual roles of RPE65 S-palmitoylation in membrane association and visual cycle function.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Higher Throughput Assays for Understanding the Pathogenicity of Variants of Unknown Significance in the RPE65 Gene.Investigative ophthalmology & visual science · 2025Article
- Higher throughput assays for understanding the pathogenicity of variants of unknown significance (VUS) in the RPE65 gene.bioRxiv : the preprint server for biology · 2025Article
- Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore.Nature chemical biology · 2024Article
- Article
- An inducible amphipathic α-helix mediates subcellular targeting and membrane binding of RPE65.Life science alliance · 2023Article
- The Amphipathic Helix in Visual Cycle Proteins: A Review.Advances in experimental medicine and biology · 2023Review
- Posttranslational modifications of proteins in diseased retina.Frontiers in cellular neuroscience · 2023Review
- Predicting potentially pathogenic effects ofJournal of enzyme inhibition and medicinal chemistry · 2022Article
- R17C Mutation in Photoreceptor Disc-Specific Protein, PRCD, Results in Additional Lipidation Altering Protein Stability and Subcellular Localization.International journal of molecular sciences · 2022Article
- Retinal pigment epithelium 65 kDa protein (RPE65): An update.Progress in retinal and eye research · 2022Review
- Light-Induced Smooth Endoplasmic Reticulum Rearrangement in a Unique Interlaced Compartmental Pattern in Macaca mulatta RPE.Investigative ophthalmology & visual science · 2021Article
- Protein Palmitoylation in Bovine Ovarian Follicle.International journal of molecular sciences · 2021Article
- A novel yeast-based high-throughput method for the identification of protein palmitoylation inhibitors.Open biology · 2021Article
- Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2.Antioxidants (Basel, Switzerland) · 2021Article
- Evolutionary aspects and enzymology of metazoan carotenoid cleavage oxygenases.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Palmitoylation of Metazoan Carotenoid Oxygenases.Molecules (Basel, Switzerland) · 2020Article
- Findings from a Genotyping Study of Over 1000 People with Inherited Retinal Disorders in Ireland.Genes · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Association with the endoplasmic reticulum (ER) membrane is a critical requirement for the catalytic function of RPE65. Several studies have investigated the nature of the RPE65-membrane interaction; however, complete understanding of its mode of membrane binding is still lacking. Previous biochemical studies suggest the membrane interaction can be partly attributed to S-palmitoylation, but the existence of RPE65 palmitoylation remains a matter of debate. Here, we re-examined RPE65 palmitoylation, and its functional consequence in the visual cycle. We clearly demonstrate that RPE65 is post-translationally modified by a palmitoyl moiety, but this is not universal (about 25% of RPE65). By extensive mutational studies we mapped the S-palmitoylation sites to residues C112 and C146. Inhibition of palmitoylation using 2-bromopalmitate and 2-fluoropalmitate completely abolish its membrane association. Furthermore, palmitoylation-deficient C112 mutants are significantly impeded in membrane association. Finally, we show that RPE65 palmitoylation level is highly regulated by lecithin:retinol acyltransferase (LRAT) enzyme. In the presence of all-trans retinol, LRAT substrate, there is a significant decrease in the level of palmitoylation of RPE65. In conclusion, our findings suggest that RPE65 is indeed a dynamically-regulated palmitoylated protein and that palmitoylation is necessary for regulating its membrane binding, and to perform its normal visual cycle function.
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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.