Identification of novel glycans with disialylated structures in α3 integrin from mouse kidney cells with the phenotype of polycystic kidney disease.
Identification of novel glycans with disialylated structures in α3 integrin from mouse kidney cells with the phenotype of polycystic kidney disease.
复制标题
鉴定来自具有多囊肾病表型的小鼠肾细胞的α3整合素中具有二唾液酸化结构的新型聚糖。
DOI：
10.1021/pr5009702
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发表时间：
2014
影响因子：
4.4
通讯作者：
Kreidberg,JordanA
中科院分区：
文献类型：
--
作者：
Zhang,AnnaFan;Wu,Shiaw-Lin;Jung,Yunjoon;Qin,Shan;Hancock,WilliamS;Kreidberg,JordanA
常染色体显性多囊肾病（ADPKD）是一种常见的遗传性疾病，由Pkd1或Pkd2基因突变引起，其中大囊肿取代正常肾脏组织，导致终末期肾脏疾病。在这项研究中，我们利用强大的纳米高效液相色谱-质谱方法来表征小鼠肾脏来源的pkd1 - / -细胞中α3整合素亚基正常和异常的n -链糖基化模式。与pkd1 - / -细胞相比，从mpkd1 +/+细胞中分离的α3整合素的Asn-925和Asn-928位点具有不同单糖组成的更高分子量的糖结构。此外，仅在pkd1 - / -细胞中观察到一种不寻常且独特的二二酸聚糖结构。因此，这些研究提示异常蛋白糖基化可能在ADPKD囊肿形成的发病机制中起作用。
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 inPkd1–/–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 fromPkd1+/+cells compared withPkd1–/–cells. In addition, an unusual and unique disialic acid glycan structure was observed solely inPkd1–/–cells. Thus, these studies suggest that abnormal protein glycosylation may have a role on the pathogenesis of cyst formation in ADPKD.