Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2011 Jan 21;2863:2224-35. doi: 10.1074/jbc.M110.149880.
Show Gene links
Show Anatomy links
Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel ROMK2 and regulates its function.
Renigunta A
,
Renigunta V
,
Saritas T
,
Decher N
,
Mutig K
,
Waldegger S
.
???displayArticle.abstract??? Tamm-Horsfall glycoprotein (THGP) or Uromodulin is a membrane protein exclusively expressed along the thick ascending limb (TAL) and early distal convoluted tubule (DCT) of the nephron. Mutations in the THGP encoding gene result in Familial Juvenile Hyperuricemic Nephropathy (FJHN), Medullary Cystic Kidney Disease type 2 (MCKD-2), and Glomerulocystic Kidney Disease (GCKD). The physicochemical and biological properties of THGP have been studied extensively, but its physiological function in the TAL remains obscure. We performed yeast two-hybrid screening employing a human kidney cDNA library and identified THGP as a potential interaction partner of the renal outer medullary potassium channel (ROMK2), a key player in the process of salt reabsorption along the TAL. Functional analysis by electrophysiological techniques in Xenopus oocytes showed a strong increase in ROMK current amplitudes when co-expressed with THGP. The effect of THGP was specific for ROMK2 and did not influence current amplitudes upon co-expression with Kir2.x, inward rectifier potassium channels related to ROMK. Single channel conductance and open probability of ROMK2 were not altered by co-expression of THGP, which instead increased surface expression of ROMK2 as determined by patch clamp analysis and luminometric surface quantification, respectively. Despite preserved interaction with ROMK2, disease-causing THGP mutants failed to increase its current amplitude and surface expression. THGP(-/-) mice exhibited increased ROMK accumulation in intracellular vesicular compartments when compared with WT animals. Therefore, THGP modulation of ROMK function confers a new role of THGP on renal ion transport and may contribute to salt wasting observed in FJHN/MCKD-2/GCKD patients.
Bachmann,
Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice.
2005, Pubmed
Bachmann,
Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice.
2005,
Pubmed
Bates,
Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication.
2004,
Pubmed
Bernascone,
Defective intracellular trafficking of uromodulin mutant isoforms.
2006,
Pubmed
Caldwell,
Degradation of endoplasmic reticulum (ER) quality control substrates requires transport between the ER and Golgi.
2001,
Pubmed
Carvalho,
Role of Tamm-Horsfall protein and uromodulin in calcium oxalate crystallization.
2002,
Pubmed
Cavallone,
Mechanism of release of urinary Tamm-Horsfall glycoprotein from the kidney GPI-anchored counterpart.
2001,
Pubmed
Chatterjee,
The GPI-anchor and protein sorting.
2001,
Pubmed
Cukras,
Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.
2002,
Pubmed
Devuyst,
Tamm-Horsfall protein or uromodulin: new ideas about an old molecule.
2005,
Pubmed
Dulawa,
Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells.
1988,
Pubmed
Gersch,
Is salt-wasting the long awaited answer to the hyperuricaemia seen in uromodulin storage diseases?
2006,
Pubmed
Haass,
Identification of yeast proteins necessary for cell-surface function of a potassium channel.
2007,
Pubmed
Hart,
Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.
2002,
Pubmed
Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed
Jennings,
Membrane targeting and secretion of mutant uromodulin in familial juvenile hyperuricemic nephropathy.
2007,
Pubmed
Koh,
Identification of SLEEPLESS, a sleep-promoting factor.
2008,
Pubmed
Kubo,
Primary structure and functional expression of a mouse inward rectifier potassium channel.
1993,
Pubmed
,
Xenbase
Köttgen,
Multiple loci associated with indices of renal function and chronic kidney disease.
2009,
Pubmed
Lu,
ROMK is required for expression of the 70-pS K channel in the thick ascending limb.
2004,
Pubmed
Malagolini,
Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall glycoprotein.
1997,
Pubmed
Mo,
Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both.
2007,
Pubmed
Mo,
Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli.
2004,
Pubmed
Morishige,
Molecular cloning, functional expression and localization of an inward rectifier potassium channel in the mouse brain.
1993,
Pubmed
,
Xenbase
Nakanishi,
Erv14 family cargo receptors are necessary for ER exit during sporulation in Saccharomyces cerevisiae.
2007,
Pubmed
Okamoto,
Glycosylphosphatidylinositol-anchored proteins are required for the transport of detergent-resistant microdomain-associated membrane proteins Tat2p and Fur4p.
2006,
Pubmed
Orskov,
Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli.
1980,
Pubmed
Pak,
Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors.
2001,
Pubmed
Powers,
Transport of axl2p depends on erv14p, an ER-vesicle protein related to the Drosophila cornichon gene product.
1998,
Pubmed
Rampoldi,
Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics.
2003,
Pubmed
Rindler,
Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol-linked membrane protein.
1990,
Pubmed
Romanenko,
Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels.
2004,
Pubmed
Sachs,
LC-MS/MS analysis of differential centrifugation fractions from native inner medullary collecting duct of rat.
2008,
Pubmed
Schmitt,
Selectively reduced expression of thick ascending limb Tamm-Horsfall protein in hypothyroid kidneys.
2004,
Pubmed
Scolari,
Uromodulin storage diseases: clinical aspects and mechanisms.
2004,
Pubmed
Simon,
Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.
1996,
Pubmed
TAMM,
Characterization and separation of an inhibitor of viral hemagglutination present in urine.
1950,
Pubmed
Takiue,
Progressive accumulation of intrinsic mouse uromodulin in the kidneys of transgenic mice harboring the mutant human uromodulin gene.
2008,
Pubmed
Wang,
Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects.
2006,
Pubmed
Welker,
Renal Na+-K+-Cl- cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent.
2008,
Pubmed
,
Xenbase
Wolf,
Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains.
2003,
Pubmed
Zuzarte,
A di-acidic sequence motif enhances the surface expression of the potassium channel TASK-3.
2007,
Pubmed
,
Xenbase
