ArticleThe Journal of biological chemistry2015
Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- A pan-vertebrate signaling motif controls the molecular function of intracellular AQP12.The Journal of cell biology · 2026Article
- Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica.Science advances · 2025Article
- Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder.International journal of molecular sciences · 2024Article
- Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica.bioRxiv : the preprint server for biology · 2024Article
- Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1-anchored membrane domains.The Journal of clinical investigation · 2023Article
- How to improve the sensitivity and specificity of cell-based assays in detecting autoantibodies in neuroimmune diseases.Annals of translational medicine · 2023Review
- Pathogenic autoantibodies in multiple sclerosis - from a simple idea to a complex concept.Nature reviews. Neurology · 2022Review
- Strategies to Screen Anti-AQP4 Antibodies from Yeast Surface Display Libraries.Antibodies (Basel, Switzerland) · 2022Article
- An Update on the Laboratory Diagnosis of Neuromyelitis Optica Spectrum Disorders.Journal of clinical neurology (Seoul, Korea) · 2022Review
- Cytoprotective IgG antibodies in sera from a subset of patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder.Scientific reports · 2021Article
- Molecular Level Characterization of Circulating Aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum Disorder.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders.Cellular & molecular immunology · 2021Review
- Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease.Clinical & translational immunology · 2021Review
- Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes.Acta neuropathologica communications · 2020Article
- Experimental animal models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress and shortcomings.Brain pathology (Zurich, Switzerland) · 2020Review
- Comparative Analysis of T-Cell Responses to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in Inflammatory Demyelinating Central Nervous System Diseases.Frontiers in immunology · 2020Article
- Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies.Immunological reviews · 2019Review
- Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production.Brain : a journal of neurology · 2019Article
- Membrane assembly of aquaporin-4 autoantibodies regulates classical complement activation in neuromyelitis optica.The Journal of clinical investigation · 2019Article
- Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat.Acta neuropathologica · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Neuromyelitis optica-immunoglobulin G (NMO-IgG) binds to aquaporin-4 (AQP4) water channels in the central nervous system leading to immune-mediated injury. We have previously demonstrated that a high proportion of CSF plasma cells of NMO patients produce antibody to the extracellular domains of the AQP4 protein and that recombinant IgG (rAb) derived from these cells recapitulate pathogenic features of disease. We performed a comprehensive mutational analysis of the three extracellular loops of the M23 isoform of human AQP4 using both serial and single point mutations, and we evaluated the effects on binding of NMO AQP4-reactive rAbs by quantitative immunofluorescence. Whereas all NMO rAbs required conserved loop C ((137)TP(138) and Val(150)) and loop E ((230)HW(231)) amino acids for binding, two broad patterns of NMO-IgG recognition could be distinguished based on differential sensitivity to loop A amino acid changes. Pattern 1 NMO rAbs were insensitive to loop A mutations and could be further discriminated by differential sensitivity to amino acid changes in loop C ((148)TM(149) and His(151)) and loop E (Asn(226) and Glu(228)). Alternatively, pattern 2 NMO rAbs showed significantly reduced binding following amino acid changes in loop A ((63)EKP(65) and Asp(69)) and loop C (Val(141), His(151), and Leu(154)). Amino acid substitutions at (137)TP(138) altered loop C conformation and abolished the binding of all NMO rAbs and NMO-IgG, indicating the global importance of loop C conformation to the recognition of AQP4 by pathogenic NMO Abs. The generation of human NMO rAbs has allowed the first high resolution mapping of extracellular loop amino acids critical for NMO-IgG binding and identified regions of AQP4 extracellular structure that may represent prime targets for drug therapy.
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