ArticleGenes & development2013
Structure and function of Norrin in assembly and activation of a Frizzled 4-Lrp5/6 complex.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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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
89 citing papers in PubMed, 132 citations in OpenAlex.
- Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modelling.Nature biomedical engineering · 2026Article
- Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.Ophthalmology and therapy · 2026Review
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Fusion Protein Technology to Enhance Pharmacological Properties of L-Asparaginases.Biomolecules · 2026Review
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Wnt/β-Catenin Pathway and Hydraulic Calcium Silicate-Based Cements: A Narrative Review.Dentistry journal · 2026Review
- A novel variant p.Y250C of FZD4 influences Norrine/β-catenin signaling pathway that associates with familial exudative vitreoretinopathy (FEVR).Scientific reports · 2026Article
- Article
- Development of Norrin-Based Protein Therapeutic for Activation of Norrin-Wnt Signaling in Human Retinal Endothelial Cells.International journal of molecular sciences · 2025Article
- Structural basis for regulation of Frizzled-4 signaling by the co-receptor Tetraspanin-12.bioRxiv : the preprint server for biology · 2025Article
- Norrie Disease: Cochlear Enhancement and Cerebellar Signal Abnormalities.AJNR. American journal of neuroradiology · 2025Article
- Targeting Wnt Signaling in Acute Lymphoblastic Leukemia.Cancers · 2025Review
- Distinct structural mechanisms of LGR4 modulation by Norrin and RSPOs in Wnt/β-catenin signaling.Nature communications · 2025Article
- Importin-alpha transports Norrin to the nucleus to promote proliferation and Notch signaling in glioblastoma stem cells.Oncogene · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Genotype-Phenotype Spectrum of eyeGENE Patients With Familial Exudative Vitreoretinopathy: Novel Variants in Norrin/β-Catenin Signaling Pathway Genes.Investigative ophthalmology & visual science · 2025Article
- Variational Approaches for Drug-Disease-Gene Links in Periodontal Inflammation.International dental journal · 2025Article
- Diabetic macular edema: Upcoming therapies.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Norrin is a cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs. It functions as an atypical Wnt ligand by specifically binding to the Frizzled 4 (Fz4) receptor. Here we report the crystal structure of Norrin, which reveals a unique dimeric structure with each monomer adopting a conserved cystine knot fold. Functional studies demonstrate that the novel Norrin dimer interface is required for Fz4 activation. Furthermore, we demonstrate that Norrin contains separate binding sites for Fz4 and for the Wnt ligand coreceptor Lrp5 (low-density lipoprotein-related protein 5) or Lrp6. Instead of inducing Fz4 dimerization, Norrin induces the formation of a ternary complex with Fz4 and Lrp5/6 by binding to their respective extracellular domains. These results provide crucial insights into the assembly and activation of the Norrin-Fz4-Lrp5/6 signaling complex.
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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.