{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:21:36Z","timestamp":1789453296873,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T00:00:00Z","timestamp":1156896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p><jats:bold>Medullary cystic kidney disease\/familial juvenile hyperuricemic nephropathy (MCKD\/FJHN) are autosomal dominant renal disorders characterized by tubulo\u2010interstitial fibrosis, hyperuricemia and medullary cysts. They are caused by mutations in the gene encoding uromodulin, the most abundant protein in urine. Uromodulin (or Tamm\u2013Horsfall protein) is a glycoprotein that is exclusively expressed by epithelial tubular cells of the thick ascending limb of Henle\u2019s 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\u2010affecting 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\u2010type 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\u2013Darby 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>","DOI":"10.1111\/j.1600-0854.2006.00481.x","type":"journal-article","created":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T12:31:27Z","timestamp":1156941087000},"page":"1567-1579","source":"Crossref","is-referenced-by-count":92,"title":["Defective Intracellular Trafficking of Uromodulin Mutant Isoforms"],"prefix":"10.1111","volume":"7","author":[{"given":"Ilenia","family":"Bernascone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Vavassori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Di Pentima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Santambrogio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lamorte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Amoroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Scolari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Marco","family":"Ghiggeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Casari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Rampoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(03)00829-1"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-74-17825"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4090"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/9.1.21"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6112"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00492456"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01919145"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00452.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00357.2003"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000088990"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00867.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522720"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2005.01483.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.12.882"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg353"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.04.003"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(03)00670-X"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021973"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000092147.83480.B5"},{"key":"e_1_2_6_21_2","first-page":"565","article-title":"Familial juvenile hyperuricemic nephropathy (FJHN): linkage analysis in 17 families, transcriptional characterization of the FJHN critical region on chromosome 16p11.2 and the analyses of uromodulin and other candidate genes","volume":"73","author":"Hodanova K","year":"2003","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00269.x"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00559.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh524"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-004-1719-2"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-6-5"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.10.092"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133039"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti486"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20810"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1200417"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81259-3"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-0854.2003.00148.x"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.459"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00845.x"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050461"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2002.31103.x"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2000.011104.x"},{"key":"e_1_2_6_40_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1681\/ASN.V82242","article-title":"New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels","volume":"8","author":"Mulders SM","year":"1997","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd052"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2004.06.056"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5722"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.683"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/47513"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20340"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-01-0033"}],"container-title":["Traffic"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0854.2006.00481.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0854.2006.00481.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T07:15:37Z","timestamp":1697267737000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0854.2006.00481.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8,30]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1111\/j.1600-0854.2006.00481.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0854.2006.00481.x","archive":["Portico"],"relation":{},"ISSN":["1398-9219","1600-0854"],"issn-type":[{"value":"1398-9219","type":"print"},{"value":"1600-0854","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8,30]]}}}