| http://purl.uniprot.org/citations/23466996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23466996 | http://www.w3.org/2000/01/rdf-schema#comment | "Uromodulin (UMOD) is synthesized in the thick ascending limb and secreted into urine as the most abundant protein. Association studies in humans suggest protective effects of UMOD against calcium-containing kidney stones. Mice carrying mutations of Umod found in human UMOD-associated kidney disease (UAKD) and Umod-deficient mice exhibit hypercalciuria. The mechanism for UMOD regulation of urinary Ca(2+) excretion is incompletely understood. We examined if UMOD regulates TRPV5 and TRPV6, channels critical for renal transcellular Ca(2+) reabsorption. Coexpression with UMOD increased whole-cell TRPV5 current density in HEK293 cells. In biotinylation studies, UMOD increased TRPV5 cell-surface abundance. Extracellular application of purified UMOD upregulated TRPV5 current density within physiological relevant concentration ranges. UMOD exerted a similar effect on TRPV6. TRPV5 undergoes constitutive caveolin-mediated endocytosis. UMOD had no effect on TRPV5 in a caveolin-1-deficient cell line. Expression of recombinant caveolin-1 in these cells restored the ability of UMOD to upregulate TRPV5. Secretion of UAKD-mutant UMOD was markedly reduced and coexpression of mutant UMOD with TRPV5 failed to increase its current. Immunofluorescent studies demonstrated lower TRPV5 expression in Umod(-/-) mice compared with wild-type. UMOD upregulates TRPV5 by acting from extracellular and by decreasing endocytosis of TRPV5. The stimulation of Ca(2+) reabsorption via TRPV5 by UMOD may contribute to protection against kidney-stone formation."xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.org/dc/terms/identifier | "doi:10.1038/ki.2013.63"xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/author | "Wolf M.T."xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/author | "Huang C.L."xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/author | "Wu X.R."xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/name | "Kidney Int"xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/pages | "130-137"xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/title | "Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis."xsd:string |
| http://purl.uniprot.org/citations/23466996 | http://purl.uniprot.org/core/volume | "84"xsd:string |
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