title: Orthogonal array formation by human aquaporin-4: examination of neuromyelitis optica-associated aquaporin-4 polymorphisms.
abstract: Pathogenic autoantibodies target aquaporin-4 (AQP4) water channels in individuals with neuromyelitis optica (NMO). Recently, allelic mutations were reported at residue 19 of AQP4 in three cases of NMO, and it was suggested that polymorphisms may influence disease by altering AQP4 supramolecular assembly into orthogonal arrays of particles (OAPs). We analyzed the determinants of OAP formation by human AQP4 to investigate the possible role of polymorphisms in NMO pathogenesis. NMO-associated mutations R19I and R19T in AQP4 did not affect OAP assembly, palmitoylation-dependent regulation of assembly, or NMO autoantibody binding. Residue-19 polymorphisms in AQP4 are thus unlikely to be disease relevant.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Crane
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Tripta
authors.initials: T
authors.lastname: Gupta
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051401:Aquaporin 4 / Q000737:chemistry* / Q000235:genetics*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D008969:Molecular Sequence Data; D009471:Neuromyelitis Optica / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D040081:Protein Array Analysis / Q000379:methods; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017433:Protein Structure, Secondary
chemical_list: D051401:Aquaporin 4; D020033:Protein Isoforms