Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein

Rooijen, Johannes J.M. van; Voskamp, Anton F.; Kamerling, Johannis P.; Vliegenthart, Johannes F.G.

doi:10.1093/glycob/9.1.21

Cited by 105 publications

(87 citation statements)

References 38 publications

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“…Deglycosylation of THP-Purified human THP was reduced and Scarboxymethylated according to van Rooijen et al (45). THP was dissolved in 1 M Tris-HCl (pH 8.25) containing a final concentration of 50 mM dithiothreitol (Sigma), 6 M guanidine chloride, and 1 mM EDTA.…”

Section: Methodsmentioning

confidence: 99%

Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors

Pak

Pu²,

Zhang³

et al. 2001

Journal of Biological Chemistry

269

201

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The adherence of uropathogenic Escherichia coli to the urothelial surface, a critical first step in the pathogenesis of urinary tract infection (UTI), is controlled by three key elements: E. coli adhesins, host receptors, and host defense mechanisms. Although much has been learned about E. coli adhesins and their urothelial receptors, little is known about the role of host defense in the adherence process. Here we show that Tamm-Horsfall protein (THP) is the principal urinary protein that binds specifically to type 1 fimbriated E. coli, the main cause of UTI. The binding was highly specific and saturable and could be inhibited by D-mannose and abolished by endoglycosidase H treatment of THP, suggesting that the binding is mediated by the high-mannose moieties of THP. It is species-conserved, occurring in both human and mouse THPs. In addition, the binding to THP was much greater with an E. coli strain bearing a phenotypic variant of the type 1 fimbrial FimH adhesin characteristic of those prevalent in UTI isolates compared with the one prevalent in isolates from the large intestine of healthy individuals. Finally, a physiological concentration of THP completely abolished the binding of type 1 fimbriated E. coli to uroplakins Ia and Ib, two putative urothelial receptors for type 1 fimbriae. These results establish, on a functional level, that THP contains conserved high-mannose moieties capable of specific interaction with type 1 fimbriae and strongly suggest that this major urinary glycoprotein is a key urinary anti-adherence factor serving to prevent type 1 fimbriated E. coli from binding to the urothelial receptors.The adhesion of Escherichia coli, the most common cause of urinary tract infection (UTI), 1 to urothelial cells is a crucially important first step in UTI pathogenesis (1-5). This adhesion process frequently requires filamentous surface appendages of uropathogenic E. coli that are called fimbriae, or pili. Epidemiological studies have shown that Ͼ90% of all E. coli isolates from UTI patients elaborate type 1 fimbriae (also named mannose-sensitive fimbriae) (4, 6, 7). Although controversies existed for several years, recent investigations have unequivocally documented the importance of type 1 fimbriae as a major urovirulence factor. For instance, of the nine most common E. coli virulence factors, the genes for type 1 fimbriae emerged as the only trait common in all 203 UTI isolates examined (8). In addition, 26% of the 203 strains were positive only for type 1 fimbrial genes and were negative for the eight other urovirulence factors tested, including P, S, and Dr fimbriae. In experimental mouse models, type 1 fimbriae were shown to be indispensable for bladder colonization and infection (9). Conversely, systemic immunization of mice with the FimH tip adhesin of type 1 fimbriae reduced bladder colonization of E. coli by 99% even in neutropenic mice, suggesting that blocking type 1 fimbriae could completely abolish E. coli adhesion (10). Further evidence supporting an important role of type 1 fimbriae ...

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Section: Methodsmentioning

confidence: 99%

Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors

Pak

Pu²,

Zhang³

et al. 2001

Journal of Biological Chemistry

269

201

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show abstract

“…More recent studies have revealed UMOD expression to be exclusive to the renal epithelial cells lining the thick ascending limb of the loop of Henle and the early distal tubule (15). UMOD protein is glycosylated at 7 of its 8 potential N-glycosylation sites (16) and is glycosylphosphatidylinositol (GPI) anchored to the luminal surface of tubules, where it is cleaved into the urine at a rate of 50 to 100 milligrams per day (17), making it the most highly secreted protein in the urine of healthy individuals (18). In urine, it is found as a high-molecular-weight polymer (relative molecular weight [Mr] 1 × 10 6 to 10 × 10 6 ) and can be dissociated into monomers of roughly 95 kDa (17).…”

Section: Introductionmentioning

confidence: 99%

Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis

Johnson

Dang

Marsh

et al. 2017

Journal of Clinical Investigation

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“…The localization of the spermligand active high-mannose-type chain in bovine ZPB and ZPC should be clarified. Besides the zona proteins, the ZP domain has been found in several proteins: TGF-b type III receptor (betaglycan) from fetal and adult tissues [28,29], uromodulin (urinary Tamm-Horsfall glycoprotein of pregnant woman) [30], the major zymogen granule membrane protein (GP-2) [31], and the proteins in the uterus and oviduct [32,33]. Furthermore, tectorins in the tectorial membranes responsible for hearing also have a ZP domain [34,35].…”

Section: Discussionmentioning

confidence: 99%

Localization of N‐linked carbohydrate chains in glycoprotein ZPA of the bovine egg zona pellucida

Ikeda

Yonezawa

Naoi

et al. 2002

European Journal of Biochemistry

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The zona pellucida, a transparent envelope surrounding the mammalian oocyte, consists of three glycoproteins, ZPA, ZPB and ZPC, and plays a role in sperm-egg interactions. In bovines, these glycoproteins cannot be separated unless the acidic N-acetyllactosamine regions of the carbohydrate chains are removed by endo-b-Galactosidase digestion. Endo-b-Galactosidase-digested ZPB retains stronger spermbinding activity than ZPC. It is still unclear whether ZPA possesses significant activity. Recently, we reported that bovine sperm binds to Man 5 GlcNAc 2 , the neutral N-linked chain in the cow zona proteins. In this study, we investigated the localization of the sperm-ligand active high-mannosetype chain and the acidic complex-type chains in bovine ZPA. Three N-glycopeptides of ZPA, containing an N-glycosylation site at Asn83, Asn191 and Asn527, respectively, were obtained from endo-b-Galactosidase-digested ZPA. Of these glycosylation sites, only Asn527 is present in the ZP domain common to all the zona proteins. The carbohydrate structures of the N-linked chains obtained from each N-glycopeptide were characterized by two-dimensional sugar mapping analysis, while considering the structures of the N-linked chains of the zona protein mixture reported previously. Acidic complex-type chains were found at all three N-glycosylation sites, while Man 5 GlcNAc 2 was found at Asn83 and Asn191, but there was very little of this spermligand active chain at Asn527 in the ZP domain of ZPA.Keywords: glycoprotein; N-linked carbohydrate chain; sperm ligand; zona pellucida; ZP domain.The mammalian oocyte is coated with a transparent matrix called the zona pellucida. This matrix plays various roles in the early phase of fertilization: species-specific sperm binding, blocking polyspermy, and protecting the embryo until implantation [1,2]. The zona is composed of three glycoproteins, called ZPA, ZPB and ZPC in the order of the size of their cDNAs [3], and their carbohydrate chains are responsible for species-specific sperm-zona binding [1,4].In the pig, the carbohydrate structures of O-linked chains of zona protein mixture [5,6] and the acidic and neutral N-linked chains of ZPB/ZPC mixture [7,8] are well characterized. Sperm-binding activity has been ascribed to the O-linked chains of the zona protein mixture [9] or to the neutral N-linked chains obtained from the ZPB/ZPC mixture [8]. We have shown that the triantennary/tetraantennary chains of the ZPB/ZPC mixture possess greater activity than the diantennary chains [10]. The triantennary/ tetraantennary chains of ZPB are localized at Asn220 in the N-terminal region [10]. Moreover, the isolated N-terminal peptide of ZPB including Asn220 has sperm-binding activity [11]. Yurewicz et al. [12] showed that ZPB and ZPC form heterocomplexes that have sperm-binding activity, but that monomeric ZPB or ZPC does not exhibit this activity. These results suggest that ZPC contributes to the expression of the sperm-binding activity of the neutral N-linked chain of ZPB. In ZPC, the triantennary/tetraante...

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Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein

Cited by 105 publications

References 38 publications

Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors

Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors

Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis

Localization of N‐linked carbohydrate chains in glycoprotein ZPA of the bovine egg zona pellucida

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