{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:09:46Z","timestamp":1789978186703,"version":"4.0.1"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,17]],"date-time":"2022-04-17T00:00:00Z","timestamp":1650153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Suntory Global Innovation Center Ltd.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Since the discovery of a specific autoantibody in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2004, the water channel aquaporin-4 (AQP4) has attracted attention as a target of autoimmune diseases of the central nervous system. In NMOSD, the autoantibody (NMO-IgG) binds to the extracellular loops of AQP4 as expressed in perivascular astrocytic end-feet and disrupts astrocytes in a complement-dependent manner. NMO-IgG is an excellent marker for distinguishing the disease from other inflammatory demyelinating diseases, such as multiple sclerosis. The unique higher-order structure of AQP4\u2014called orthogonal arrays of particles (OAPs)\u2014as well as its subcellular localization may play a crucial role in the pathogenesis of the disease. Recent studies have also demonstrated complement-independent cytotoxic effects of NMO-IgG. Antibody-induced endocytosis of AQP4 has been suggested to be involved in this mechanism. This review focuses on the binding properties of antibodies that recognize the extracellular region of AQP4 and the characteristics of AQP4 that are implicated in the pathogenesis of NMOSD.<\/jats:p>","DOI":"10.3390\/biom12040591","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T04:21:28Z","timestamp":1650255688000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6163-8794","authenticated-orcid":false,"given":"Yoichiro","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Keio University Global Research Institute, Tokyo 108-8345, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Keio University Global Research Institute, Tokyo 108-8345, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","article-title":"International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","article-title":"A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1212\/01.WNL.0000289761.64862.ce","article-title":"Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica","volume":"69","author":"Hinson","year":"2007","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/ana.21837","article-title":"Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo","volume":"66","author":"Bradl","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.21802","article-title":"Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica","volume":"66","author":"Bennett","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2009.06.085","article-title":"Neuromyelitis optica: Passive transfer to rats by human immunoglobulin","volume":"386","author":"Kinoshita","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jneuroim.2009.07.014","article-title":"Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: An in vitro study","volume":"215","author":"Sabater","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/brain\/awp309","article-title":"Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice","volume":"133","author":"Saadoun","year":"2010","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/ana.22551","article-title":"Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanisms","volume":"70","author":"Zhang","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00401-018-1950-8","article-title":"Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat","volume":"137","author":"Hillebrand","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/brain\/awl371","article-title":"Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis","volume":"130","author":"Roemer","year":"2007","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/brain\/awm047","article-title":"Loss of aquaporin 4 in lesions of neuromyelitis optica: Distinction from multiple sclerosis","volume":"130","author":"Misu","year":"2007","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41582-021-00568-8","article-title":"Hope for patients with neuromyelitis optica spectrum disorders\u2014From mechanisms to trials","volume":"17","author":"Pittocks","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.1007\/s00415-020-10235-5","article-title":"Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder","volume":"268","author":"Illes","year":"2021","journal-title":"J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12974-021-02249-1","article-title":"Neuromyelitis optica spectrum disorders: From pathophysiology to therapeutic strategies","volume":"18","author":"Contentti","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00401-017-1734-6","article-title":"Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica","volume":"134","author":"Tradtrantip","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s12974-018-1333-z","article-title":"Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica","volume":"15","author":"Duan","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.4049\/jimmunol.181.8.5730","article-title":"Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment","volume":"18","author":"Vincent","year":"2008","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00401-012-0986-4","article-title":"Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss","volume":"123","author":"Ratelade","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1172\/JCI67554","article-title":"Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica","volume":"123","author":"Zhang","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00401-013-1172-z","article-title":"Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis optica","volume":"126","author":"Ratelade","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s40478-015-0259-2","article-title":"Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody","volume":"3","author":"Kurosawa","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s40478-019-0766-7","article-title":"Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody-dependent cellular cytotoxicity","volume":"7","author":"Duan","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20081241","article-title":"Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2","volume":"205","author":"Hinson","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1093\/brain\/awq177","article-title":"Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury","volume":"133","author":"Marignier","year":"2010","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1073\/pnas.1701960114","article-title":"Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor","volume":"114","author":"Hinson","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/glia.22635","article-title":"Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures","volume":"62","author":"Howe","year":"2014","journal-title":"Glia"},{"key":"ref_29","first-page":"4025","article-title":"Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1016\/S0021-9258(17)37486-0","article-title":"Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues","volume":"269","author":"Hasegawa","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13052","DOI":"10.1073\/pnas.91.26.13052","article-title":"Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance","volume":"91","author":"Jung","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","first-page":"F775","article-title":"Distribution of aquaporin-4 water channel expression within rat kidney","volume":"269","author":"Terris","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.1073\/pnas.92.10.4328","article-title":"Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes","volume":"92","author":"Frigeri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1242\/jcs.108.9.2993","article-title":"Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues","volume":"108","author":"Frigeri","year":"1995","journal-title":"J. Cell Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/0014-5793(96)00092-0","article-title":"A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach","volume":"381","author":"Misaka","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"C1549","DOI":"10.1152\/ajpcell.1997.273.5.C1549","article-title":"Aquaporins in complex tissues. II. Subcellular distribution in respiratory and glandular tissues of rat","volume":"273","author":"Nielsen","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1172\/JCI2545","article-title":"Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle","volume":"102","author":"Frigeri","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1523\/JNEUROSCI.18-07-02506.1998","article-title":"Aquaporin-4 water channel protein in the rat retina and optic nerve: Polarized expression in M\u00fcller cells and fibrous astrocytes","volume":"18","author":"Nagelhus","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1046\/j.1460-9568.1998.00360.x","article-title":"Select types of supporting cell in the inner ear express aquaporin-4 water channel protein","volume":"10","author":"Takumi","year":"1998","journal-title":"Eur. J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"C621","DOI":"10.1152\/ajpcell.1999.276.3.C621","article-title":"Expression and localization of aquaporins in rat gastrointestinal tract","volume":"276","author":"Koyama","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0014-5793(99)01256-9","article-title":"High-resolution immunogold cytochemistry indicates that AQP4 is concentrated along the basal membrane of parietal cell in rat stomach","volume":"459","author":"Fujita","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C1108","DOI":"10.1152\/ajpcell.2000.278.6.C1108","article-title":"Skeletal muscle function and water permeability in aquaporin-4 deficient mice","volume":"278","author":"Yang","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.bbrc.2014.08.026","article-title":"Expression and localization of aquaporin-4 in sensory ganglia","volume":"451","author":"Kato","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997","article-title":"Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain","volume":"17","author":"Nielsen","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00031.2020","article-title":"Fluid Transport in the Brain","volume":"102","author":"Rasmussen","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11156","DOI":"10.1021\/bi990941s","article-title":"Heterotetrameric composition of aquaporin-4 water channels","volume":"38","author":"Neely","year":"1999","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.jmb.2005.10.081","article-title":"Implications of the aquaporin-4 structure on array formation and cell adhesion","volume":"355","author":"Hiroaki","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1074\/jbc.271.9.4577","article-title":"The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells","volume":"271","author":"Yang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1242\/jcs.110.22.2855","article-title":"Absence of orthogonal arrays in kidney, brain and muscle from transgenic knockout mice lacking water channel aquaporin-4","volume":"110","author":"Verbavatz","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11981","DOI":"10.1073\/pnas.95.20.11981","article-title":"Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord","volume":"95","author":"Rash","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1021\/bi702146k","article-title":"The molecular composition of square arrays","volume":"47","author":"Sorbo","year":"2008","journal-title":"Biochemistry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.neuroscience.2010.02.008","article-title":"Higher order structure of aquaporin-4","volume":"168","author":"Nicchia","year":"2010","journal-title":"Neuroscience"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"22907","DOI":"10.1074\/jbc.270.39.22907","article-title":"cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units","volume":"270","author":"Yang","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10908","DOI":"10.1073\/pnas.93.20.10908","article-title":"The human AQP4 gene: Definition of the locus encoding two water channel polypeptides in brain","volume":"93","author":"Lu","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1006\/geno.1997.4641","article-title":"Cloning and chromosomal localization of mouse aquaporin 4: Exclusion of a candidate mutant phenotype, ataxia","volume":"41","author":"Turtzo","year":"1997","journal-title":"Genomics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13609","DOI":"10.1073\/pnas.2235843100","article-title":"Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms","volume":"100","author":"Furman","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"F501","DOI":"10.1152\/ajprenal.00439.2003","article-title":"Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells","volume":"287","author":"Silberstein","year":"2004","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1021\/bi802231q","article-title":"Roles of aquaporin-4 isoforms and amino acids in square array assembly","volume":"48","author":"Strand","year":"2009","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.bbamem.2007.12.007","article-title":"Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-terminal cysteine residues","volume":"1778","author":"Suzuki","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"35850","DOI":"10.1074\/jbc.M109.071670","article-title":"Live cell analysis of aquaporin-4 m1\/m23 interactions and regulated orthogonal array assembly in glial cells","volume":"284","author":"Crane","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1242\/jcs.042341","article-title":"Determinants of aquaporin-4 assembly in orthogonal arrays revealed by live-cell single-molecule fluorescence imaging","volume":"122","author":"Crane","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1600-0854.2011.01299.x","article-title":"Post-Golgi supramolecular assembly of aquaporin-4 in orthogonal arrays","volume":"13","author":"Rossi","year":"2012","journal-title":"Traffic"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/glia.23909","article-title":"Orthogonal arrays of particle assembly are essential for normal aquaporin-4 expression level in the brain","volume":"69","author":"Cibelli","year":"2021","journal-title":"Glia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1002\/glia.24032","article-title":"Regulation of aquaporin-4 expression in the central nervous system investigated using M23-AQP4 null mouse","volume":"69","author":"Pisani","year":"2021","journal-title":"Glia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1111\/j.1460-9568.1996.tb01568.x","article-title":"Dystroglycan in the cerebellum is a laminin alpha 2-chain binding protein at the glial-vascular interface and is expressed in Purkinje cells","volume":"8","author":"Tian","year":"1997","journal-title":"Eur. J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1083\/jcb.147.3.645","article-title":"Different dystrophin-like complexes are expressed in neurons and glia","volume":"147","author":"Blake","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1083\/jcb.145.2.391","article-title":"A PDZ-containing scaffold related to the dystrophin complex at the basolateral membrane of epithelial cells","volume":"145","author":"Kachinsky","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1111\/j.1471-4159.2008.05302.x","article-title":"Expression of multiple AQP4 pools in the plasma membrane and their association with the dystrophin complex","volume":"105","author":"Nicchia","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/glia.20661","article-title":"Dystrophin-dependent and -independent AQP4 pools are expressed in the mouse brain","volume":"56","author":"Nicchia","year":"2008","journal-title":"Glia"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1083\/jcb.200106158","article-title":"In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4","volume":"155","author":"Adams","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14108","DOI":"10.1073\/pnas.241508198","article-title":"Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein","volume":"98","author":"Neely","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ygeno.2007.12.003","article-title":"New isoforms of rat Aquaporin-4","volume":"91","author":"Moe","year":"2008","journal-title":"Genomics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1006\/geno.1996.0214","article-title":"Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel","volume":"33","author":"Ma","year":"1996","journal-title":"Genomics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/glia.21177","article-title":"Aquaporin-4 Mz isoform: Brain expression, supramolecular assembly and neuromyelitis optica antibody binding","volume":"59","author":"Rossi","year":"2011","journal-title":"Glia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1203\/00006450-200009000-00012","article-title":"Identification of a new form of AQP4 mRNA that is developmentally expressed in mouse brain","volume":"48","author":"Zelenin","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_76","first-page":"425","article-title":"Identification of new M23A mRNA of mouse aquaporin-4 expressed in brain, liver, and kidney","volume":"77","author":"Alikina","year":"2012","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/j.1471-4159.2012.07652.x","article-title":"An astrocyte-specific enhancer of the aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements","volume":"120","author":"Abe","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1002\/1873-3468.12910","article-title":"The dual effects of the astrocyte-specific enhancer of the AQP4 M1 promoter","volume":"591","author":"Abe","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12006","DOI":"10.1074\/jbc.M111.280701","article-title":"MicroRNA-130a represses transcriptional activity of aquaporin 4 M1 promoter","volume":"287","author":"Sepramaniam","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1091\/mbc.e13-06-0331","article-title":"A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: A new mechanism to regulate water permeability","volume":"25","author":"Pisani","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.1074\/jbc.M109.069245","article-title":"Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: Implication in orthogonal array formation and neuromyelitis optica antibody interaction","volume":"285","author":"Rossi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1002\/glia.21234","article-title":"Translational regulation mechanisms of aquaporin-4 supramolecular organization in astrocytes","volume":"59","author":"Pisani","year":"2011","journal-title":"Glia"},{"key":"ref_83","first-page":"77","article-title":"The binding property of a monoclonal antibody against the extracellular domains of aquaporin-4 directs aquaporin-4 toward endocytosis","volume":"7","author":"Huang","year":"2016","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/glia.23126","article-title":"Translational readthrough generates new astrocyte AQP4 isoforms that modulate supramolecular clustering, glial endfeet localization, and water transport","volume":"65","author":"Pisani","year":"2017","journal-title":"Glia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-019-0707-5","article-title":"AQP4ex is crucial for the anchoring of AQP4 at the astrocyte end-feet and for neuromyelitis optica antibody binding","volume":"7","author":"Palazzo","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Palazzo, C., Abbrescia, P., Valente, O., Nicchia, G.P., Banitalebi, S., Amiry-Moghaddam, M., Trojano, M., and Frigeri, A. (2020). Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041531"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"29223","DOI":"10.1074\/jbc.M110.144576","article-title":"MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia","volume":"285","author":"Sepramaniam","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbrc.2008.09.155","article-title":"Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes","volume":"377","author":"Kadohira","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"C957","DOI":"10.1152\/ajpcell.00182.2014","article-title":"AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at COOH-terminal serine residues","volume":"307","author":"Assentoft","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/glia.20855","article-title":"Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies","volume":"57","author":"Nicchia","year":"2009","journal-title":"Glia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1002\/glia.22417","article-title":"Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma membrane M1\/M23 isoform content, or supramolecular assembly","volume":"60","author":"Rossi","year":"2012","journal-title":"Glia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jneuroim.2013.03.003","article-title":"Establishment of monoclonal antibodies against the extracellular domain that block binding of NMO-IgG to AQP4","volume":"260","author":"Miyazaki","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1007\/s12035-021-02491-x","article-title":"Aquaporin-4 Removal from the Plasma Membrane of Human M\u00fcller Cells by AQP4-IgG from patients with neuromyelitis optica induces changes in cell volume homeostasis: The first step of retinal injury?","volume":"58","author":"Netti","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jneuroim.2009.04.001","article-title":"Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica","volume":"211","author":"Tani","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"16516","DOI":"10.1074\/jbc.M111.227298","article-title":"Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1\/M23 isoforms and orthogonal arrays","volume":"286","author":"Crane","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9216","DOI":"10.1074\/jbc.M110.123000","article-title":"Identification of two major conformational aquaporin-4 epitopes for neuromyelitis optica autoantibody binding","volume":"286","author":"Pisani","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jaut.2012.07.008","article-title":"Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays","volume":"40","author":"Iorio","year":"2013","journal-title":"J. Autoimmun."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mader, S., Lutterotti, A., Di Pauli, F., Kuenz, B., Schanda, K., Aboul-Enein, F., Khalil, M., Storch, M.K., Jarius, S., and Kristoferitsch, W. (2010). Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010455"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"13829","DOI":"10.1074\/jbc.M112.344325","article-title":"Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays","volume":"287","author":"Phuan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1073\/pnas.1109980108","article-title":"Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes","volume":"109","author":"Hinson","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/ana.22657","article-title":"Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica","volume":"71","author":"Tradtrantip","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"107827","DOI":"10.1016\/j.neuropharm.2019.107827","article-title":"Affinity-matured \u2018aquaporumab\u2019 anti-aquaporin-4 antibody for therapy of seropositive neuromyelitis optica spectrum disorders","volume":"162","author":"Duan","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jim.2007.02.005","article-title":"Viral envelope protein gp64 transgenic mouse facilitates the generation of monoclonal antibodies against exogenous membrane proteins displayed on baculovirus","volume":"322","author":"Saitoh","year":"2007","journal-title":"J. Immunol. Methods"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/bph.13340","article-title":"High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with the neuromyelitis optica autoantibody, NMO-IgG","volume":"173","author":"Takai","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mcn.2013.02.002","article-title":"Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin","volume":"56","author":"Abe","year":"2013","journal-title":"Mol. Cell Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1089\/mab.2013.0007","article-title":"A novel monoclonal antibody against the C-terminal region of aquaporin-4","volume":"32","author":"Ramadhanti","year":"2013","journal-title":"Monoclon. Antib. Immunodiagn. Immunother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1091\/mbc.e08-03-0322","article-title":"Aquaporin-4 dynamics in orthogonal arrays in live cells visualized by quantum dot single particle tracking","volume":"19","author":"Crane","year":"2008","journal-title":"Mol. Biol. 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