{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361981471078920192.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1111/j.1600-0854.2006.00481.x"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1600-0854.2006.00481.x"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0854.2006.00481.x"}}],"dc:title":[{"@value":"Defective Intracellular Trafficking of Uromodulin Mutant Isoforms"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p><jats:bold>Medullary cystic kidney disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) are autosomal dominant renal disorders characterized by tubulo‐interstitial fibrosis, hyperuricemia and medullary cysts. They are caused by mutations in the gene encoding uromodulin, the most abundant protein in urine. Uromodulin (or Tamm–Horsfall protein) is a glycoprotein that is exclusively expressed by epithelial tubular cells of the thick ascending limb of Henle’s loop and distal convoluted tubule. To date, 37 different uromodulin mutations have been described in patients with MCKD/FJHN. Interestingly, 60% of them involve one of the 48 conserved cysteine residues. We have previously shown that cysteine‐affecting mutations could lead to partial endoplasmic reticulum (ER) retention. In this study, as a further step in understanding uromodulin biology in health and disease, we provide the first extensive study of intracellular trafficking and subcellular localization of wild‐type and mutant uromodulin isoforms. We analyzed a set of 12 different uromodulin mutations that were representative of the different kind of mutations identified so far by different experimental approaches (immunofluorescence, electron microscopy, biochemistry and <jats:italic>in vivo</jats:italic> imaging) in transiently transfected HEK293 and Madin–Darby canine kidney cells. We assessed protein processing in the secretory pathway and could demonstrate that although to different extent, all uromodulin mutations lead to defective ER to Golgi protein transport, suggesting a common pathogenetic mechanism in MCKD/FJHN.</jats:bold></jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381981471078920198","@type":"Researcher","foaf:name":[{"@value":"Ilenia Bernascone"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920194","@type":"Researcher","foaf:name":[{"@value":"Stefano Vavassori"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920195","@type":"Researcher","foaf:name":[{"@value":"Alessio Di Pentima"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920201","@type":"Researcher","foaf:name":[{"@value":"Sara Santambrogio"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920192","@type":"Researcher","foaf:name":[{"@value":"Giuseppe Lamorte"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920193","@type":"Researcher","foaf:name":[{"@value":"Antonio Amoroso"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920197","@type":"Researcher","foaf:name":[{"@value":"Francesco Scolari"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920200","@type":"Researcher","foaf:name":[{"@value":"Gian Marco Ghiggeri"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920202","@type":"Researcher","foaf:name":[{"@value":"Giorgio Casari"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920199","@type":"Researcher","foaf:name":[{"@value":"Roman Polishchuk"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981471078920196","@type":"Researcher","foaf:name":[{"@value":"Luca Rampoldi"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13989219"},{"@type":"EISSN","@value":"16000854"}],"prism:publicationName":[{"@value":"Traffic"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2006-08-30","prism:volume":"7","prism:number":"11","prism:startingPage":"1567","prism:endingPage":"1579"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1600-0854.2006.00481.x"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0854.2006.00481.x"}],"createdAt":"2006-08-30","modifiedAt":"2023-10-14","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360572092659628032","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Vasopressin Induces Urinary Uromodulin Secretion By Activating PKA (Protein Kinase A)"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204625798016","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Progressive Accumulation of Intrinsic Mouse Uromodulin in the Kidneys of Transgenic Mice Harboring the Mutant Human Uromodulin Gene"}]},{"@id":"https://cir.nii.ac.jp/crid/2051714792015453440","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Hsp70 promotes maturation of uromodulin mutants that cause familial juvenile hyperuricemic nephropathy and suppresses cellular damage"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1111/j.1600-0854.2006.00481.x"},{"@type":"CROSSREF","@value":"10.1007/s10157-022-02196-y_references_DOI_Lz7S6kSoPOAP7yTCxGPZOkLFNm5"},{"@type":"CROSSREF","@value":"10.1248/bpb.31.405_references_DOI_Lz7S6kSoPOAP7yTCxGPZOkLFNm5"},{"@type":"CROSSREF","@value":"10.1161/hypertensionaha.121.17127_references_DOI_Lz7S6kSoPOAP7yTCxGPZOkLFNm5"}]}