title: Identification of novel glycans with disialylated structures in α3 integrin from mouse kidney cells with the phenotype of polycystic kidney disease.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder caused by mutations in the Pkd1 or Pkd2 genes, in which large cysts replace normal kidney tissue, leading to end-stage kidney disease. In this study we have utilized a powerful nano-HPLC-mass spectrometric approach to characterize patterns of normal and abnormal N-linked glycosylation of α3 integrin subunit in Pkd1(-/-) cells derived from mouse kidneys. Higher molecular weight glycan structures with a different monosaccharide composition were observed at two sites, namely, Asn-925 and Asn-928 sites in α3 integrin isolated from Pkd1(+/+) cells compared with Pkd1(-/-) cells. In addition, an unusual and unique disialic acid glycan structure was observed solely in Pkd1(-/-) cells. Thus, these studies suggest that abnormal protein glycosylation may have a role on the pathogenesis of cyst formation in ADPKD.
authors.affiliation: Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Anna Fan
authors.initials: AF
authors.lastname: Zhang
authors.forename: Shiaw-Lin
authors.initials: SL
authors.lastname: Wu
authors.forename: Yunjoon
authors.initials: Y
authors.lastname: Jung
authors.forename: Shan
authors.initials: S
authors.lastname: Qin
authors.forename: William S
authors.initials: WS
authors.lastname: Hancock
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Kreidberg
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D047468:Immunoprecipitation; D039422:Integrin alpha3 / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D007690:Polycystic Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000302:isolation & purification / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D050396:TRPP Cation Channels / Q000235:genetics
chemical_list: D039422:Integrin alpha3; D011134:Polysaccharides; D012794:Sialic Acids; D050396:TRPP Cation Channels
keywords: N-linked glycosylation; Pkd1+/+ cells; Pkd1−/− cells; glycans; glycopeptide analysis; polycystic kidney disease; site-specific identification; α3 integrin