ArticleThe Journal of clinical investigation2011
Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 109 citations in OpenAlex.
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- Advances in ciliary proteomics - towards cracking the hidden proteome code of cilia.Journal of cell science · 2025Review
- Associations between RetNet gene polymorphisms and the efficacy of orthokeratology for myopia control: a retrospective clinical study.Eye and vision (London, England) · 2025Article
- Intraflagellar transport: A critical player in photoreceptor development and the pathogenesis of retinal degenerative diseases.Cytoskeleton (Hoboken, N.J.) · 2024Review
- Human retina-in-a-dish: Unlocking the potential to study mechanisms of inherited retinal disease.Molecular therapy. Methods & clinical development · 2023Article
- Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.Investigative ophthalmology & visual science · 2023Article
- CRISPR-Cas9 correction of a nonsense mutation inMolecular therapy. Methods & clinical development · 2023Article
- Gene augmentation of LCA5-associated Leber congenital amaurosis ameliorates bulge region defects of the photoreceptor ciliary axoneme.JCI insight · 2023Article
- Stargardt-like Clinical Characteristics and Disease Course Associated with Variants in theGenes · 2023Article
- Paralog-specific TTC30 regulation of Sonic hedgehog signaling.Frontiers in molecular biosciences · 2023Article
- Cargo adapters expand the transport range of intraflagellar transport.Journal of cell science · 2022Review
- Interactions between C8orf37 and FAM161A, Two Ciliary Proteins Essential for Photoreceptor Survival.International journal of molecular sciences · 2022Article
- The interaction between LC8 and LCA5 reveals a novel oligomerization function of LC8 in the ciliary-centrosome system.Scientific reports · 2022Article
- TTC30A and TTC30B Redundancy Protects IFT Complex B Integrity and Its Pivotal Role in Ciliogenesis.Genes · 2022Article
- The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration.PLoS biology · 2022Article
- On the Wrong Track: Alterations of Ciliary Transport in Inherited Retinal Dystrophies.Frontiers in cell and developmental biology · 2021Review
- Limited time window for retinal gene therapy in a preclinical model of ciliopathy.Human molecular genetics · 2020Article
- Treatment Potential for LCA5-Associated Leber Congenital Amaurosis.Investigative ophthalmology & visual science · 2020Article
- Voretigene Neparvovec and Gene Therapy for Leber's Congenital Amaurosis: Review of Evidence to Date.The application of clinical genetics · 2020Review
- Functional Genomics of the Retina to Elucidate its Construction and Deconstruction.International journal of molecular sciences · 2019Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 5 countries.
Funding
Abstract
The mutations that cause Leber congenital amaurosis (LCA) lead to photoreceptor cell death at an early age, causing childhood blindness. To unravel the molecular basis of LCA, we analyzed how mutations in LCA5 affect the connectivity of the encoded protein lebercilin at the interactome level. In photoreceptors, lebercilin is uniquely localized at the cilium that bridges the inner and outer segments. Using a generally applicable affinity proteomics approach, we showed that lebercilin specifically interacted with the intraflagellar transport (IFT) machinery in HEK293T cells. This interaction disappeared when 2 human LCA-associated lebercilin mutations were introduced, implicating a specific disruption of IFT-dependent protein transport, an evolutionarily conserved basic mechanism found in all cilia. Lca5 inactivation in mice led to partial displacement of opsins and light-induced translocation of arrestin from photoreceptor outer segments. This was consistent with a defect in IFT at the connecting cilium, leading to failure of proper outer segment formation and subsequent photoreceptor degeneration. These data suggest that lebercilin functions as an integral element of selective protein transport through photoreceptor cilia and provide a molecular demonstration that disrupted IFT can lead to LCA.
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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.