{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:19:02Z","timestamp":1768745942796,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T00:00:00Z","timestamp":1508457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuromyelitis optica (<jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>) is an autoimmune demyelinating disease of the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) caused by autoantibodies (<jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>\u2010IgG) against the water channel aquaporin\u20104 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4). Though <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 is also expressed outside the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, for example in skeletal muscle, patients with <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> generally do not show clinical\/diagnostic evidence of skeletal muscle damage. Here, we have evaluated whether <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 supramolecular organization is at the basis of the different tissue susceptibility. Using immunofluorescence we found that while the sera of our cohort of patients with <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> gave typical perivascular staining in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, they were largely negative in the skeletal muscle. This conclusion was obtained using human, rat and mouse skeletal muscle including the <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mouse. A biochemical analysis using a new size exclusion chromatography approach for <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 suprastructure fractionation revealed substantial differences in supramolecular <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 assemblies and isoform abundance between brain and skeletal muscle matching a lower binding affinity of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>\u2010IgG to muscle compared to the brain. Super\u2010resolution microscopy analysis with g\u2010<jats:styled-content style=\"fixed-case\">STED<\/jats:styled-content> revealed different <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 organization in native tissues, while in the brain perivascular astrocyte endfoot membrane <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 was mainly organized in large interconnected and raft\u2010like clusters, in the sarcolemma of fast\u2010twitch fibres <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 aggregates often appeared as small, relatively isolated linear entities. In conclusion, our results provide evidence that <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4 supramolecular structure is different in brain and skeletal muscle, which is likely to result in different tissues susceptibility to the <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> disease.<\/jats:p>","DOI":"10.1111\/jcmm.13401","type":"journal-article","created":{"date-parts":[[2017,10,21]],"date-time":"2017-10-21T04:08:43Z","timestamp":1508558923000},"page":"1236-1246","source":"Crossref","is-referenced-by-count":16,"title":["Supramolecular aggregation of aquaporin\u20104 is different in muscle and brain: correlation with tissue susceptibility in neuromyelitis optica"],"prefix":"10.1111","volume":"22","author":[{"given":"Stefania","family":"Rosito","sequence":"first","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-514X","authenticated-orcid":false,"given":"Grazia Paola","family":"Nicchia","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"},{"name":"Dominick P. Purpura Department of Neuroscience Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Palazzo","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"},{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lia","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Buccoliero","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"},{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-117X","authenticated-orcid":false,"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Svelto","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Biopharmaceutic University of Bari \u201cAldo Moro\u201d Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Trojano","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-2934","authenticated-orcid":false,"given":"Antonio","family":"Frigeri","sequence":"additional","affiliation":[{"name":"Dominick P. 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