ArticleInvestigative ophthalmology & visual science2014
Mutant ELOVL4 that causes autosomal dominant stargardt-3 macular dystrophy is misrouted to rod outer segment disks.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Associations of human retinal very long-chain polyunsaturated fatty acids with dietary lipid biomarkers.Journal of lipid research · 2016Trial
- Lipid homeostasis plays a critical role in inherited and acquired retinal diseases.Communications biology · 2026Review
- Systematic review:Frontiers in medicine · 2025Review
- Updates on Emerging Interventions for Autosomal RecessiveJournal of clinical medicine · 2023Review
- Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment.Antioxidants (Basel, Switzerland) · 2023Review
- ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function.Progress in retinal and eye research · 2019Review
- Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection.Molecular aspects of medicine · 2018Review
- Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3).Scientific reports · 2018Article
- Article
- Elovl4 5-bp deletion does not accelerate cone photoreceptor degeneration in an all-cone mouse.PloS one · 2018Article
- Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity.Scientific reports · 2017Article
- Retinal Degeneration and Regeneration-Lessons From Fishes and Amphibians.Current pathobiology reports · 2017Review
- Mouse Models of Stargardt 3 Dominant Macular Degeneration.Advances in experimental medicine and biology · 2016Article
- Photoreceptors at a glance.Journal of cell science · 2015Review
- Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival.Nature communications · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeAutosomal dominant Stargardt macular dystrophy caused by mutations in the Elongation of Very Long Chain fatty acids (ELOVL4) gene results in macular degeneration, leading to early childhood blindness. Transgenic mice and pigs expressing mutant ELOVL4 develop progressive photoreceptor degeneration. The mechanism by which these mutations cause macular degeneration remains unclear, but have been hypothesized to involve the loss of an ER-retention dilysine motif located in the extreme C-terminus. Dominant negative mechanisms and reduction in retinal polyunsaturated fatty acids also have been suggested. To understand the molecular mechanisms involved in disease progression in vivo, we addressed the hypothesis that the disease-linked C-terminal truncation mutant of ELOVL4 exerts a dominant negative effect on wild-type (WT) ELOVL4, altering its subcellular localization and function, which subsequently induces retinal degeneration and loss of vision.
methodsWe generated transgenic Xenopus laevis that overexpress HA-tagged murine ELOVL4 variants in rod photoreceptors.
resultsTagged or untagged WT ELOVL4 localized primarily to inner segments. However, the mutant protein lacking the dilysine motif was mislocalized to post-Golgi compartments and outer segment disks. Coexpression of mutant and WT ELOVL4 in rods did not result in mislocalization of the WT protein to outer segments or in the formation of aggregates. Full-length HA-tagged ELOVL4 lacking the dilysine motif (K308R/K310R) necessary for targeting the WT ELOVL4 protein to the endoplasmic reticulum was similarly mislocalized to outer segments.
conclusionsWe propose that expression and outer segment mislocalization of the disease-linked 5-base-pair deletion mutant ELOVL4 protein alters photoreceptor structure and function, which subsequently results in retinal degeneration, and suggest three possible mechanisms by which mutant ELOVL4 may induce retinal degeneration in STGD3.
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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.