ArticleProceedings of the National Academy of Sciences of the United States of America2010
RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 101 citations in OpenAlex.
- Cellular Identity Crisis: RD3 Loss Fuels Plasticity and Immune Silence in Progressive Neuroblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genome-wide association study identifies novel variants in olfactory, vitamin A, vitamin B, and cadherin pathways associated with learning and memory.Scientific reports · 2025Article
- A multilayered gap junction network is essential for social decision-making.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Retinal degeneration protein 3 mutants are associated with cell-cycle arrest and apoptosis.Cell death discovery · 2025Article
- Limited Added Diagnostic Value of Whole Genome Sequencing in Genetic Testing of Inherited Retinal Diseases in a Swiss Patient Cohort.International journal of molecular sciences · 2024Article
- In vivo CRISPR screening directly targeting testicular cells.Cell genomics · 2024Article
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- Structural view of G protein-coupled receptor signaling in the retinal rod outer segment.Trends in biochemical sciences · 2023Review
- Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids.Stem cell reports · 2023Article
- The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State.International journal of molecular sciences · 2022Article
- Structural basis of retinal membrane guanylate cyclase regulation by GCAP1 and RD3.Frontiers in molecular neuroscience · 2022Review
- Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue.Frontiers in molecular neuroscience · 2022Article
- Regulation of retinal membrane guanylyl cyclase (RetGC) by negative calcium feedback and RD3 protein.Pflugers Archiv : European journal of physiology · 2021Review
- The parasite Schistocephalus solidus secretes proteins with putative host manipulation functions.Parasites & vectors · 2021Article
- Review
- Zebrafish Models of Photoreceptor Dysfunction and Degeneration.Biomolecules · 2021Review
- Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art.Frontiers in medicine · 2021Review
- Article
- Two clusters of surface-exposed amino acid residues enable high-affinity binding of retinal degeneration-3 (RD3) protein to retinal guanylyl cyclase.The Journal of biological chemistry · 2020Article
- RNA-based therapies in animal models of Leber congenital amaurosis causing blindness.Precision clinical medicine · 2020Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Guanylate cyclases, GC1 and GC2, are localized in the light-sensitive outer segment compartment of photoreceptor cells, where they play a crucial role in phototransduction by catalyzing the synthesis of cGMP, the second messenger of phototransduction, and regulating intracellular Ca(2+) levels in combination with the cGMP-gated channel. Mutations in GC1 are known to cause Leber congenital amaurosis type 1 (LCA1), a childhood disease associated with severe vision loss. Although the enzymatic and regulatory properties of guanylate cyclases have been studied extensively, the molecular determinants responsible for their trafficking in photoreceptors remain unknown. Here we show that RD3, a protein of unknown function encoded by a gene associated with photoreceptor degeneration in humans with Leber congenital amaurosis type 12 (LCA12), the rd3 mouse, and rcd2 collie, colocalizes and interacts with GC1 and GC2 in rod and cone photoreceptor cells of normal mice. GC1 and GC2 are undetectable in photoreceptors of the rd3 mouse deficient in RD3 by immunofluorescence microscopy. Cell expression studies show that RD3 mediates the export of GC1 from the endoplasmic reticulum to endosomal vesicles, and that the C terminus of GC1 is required for RD3 binding. Our results indicate that photoreceptor degeneration in the rd3 mouse, rcd2 dog, and LCA12 patients is caused by impaired RD3-mediated guanylate cyclase expression and trafficking. The resulting deficiency in cGMP synthesis and the constitutive closure of cGMP-gated channels might cause a reduction in intracellular Ca(2+) to a level below that required for long-term photoreceptor cell survival.
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