N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability

doi:10.3390/ijms17060937

淡江大學機構典藏 > 理學院 > 化學學系暨研究所 > 期刊論文 > Item 987654321/107112

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/107112

题名:	N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability
作者:	Chang, Chiung-Fang;Hsu, Li-Sung;Weng, Chieh-Yu;Chen, Chih-Kai;Wang, Shu-Ying;Chou, Yi-Hwa;Liu, Yan-Yu;Yuan, Zi-Xiu;Huang, Wen-Ying;Lin, Ho;Chen, Yau-Hung;Tsai, Jen-Ning
关键词:	R-spondin 1;N-glycosylation;secretion;stability;Wnt signaling
日期:	2016-06-27
上传时间:	2016-08-15
出版者:	M D P I AG
摘要:	R-spondin 1 (Rspo1) plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1) domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER) quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1.
關聯:	International Journal of Molecular Sciences 17(6), pp.937
DOI:	10.3390/ijms17060937
显示于类别:	[化學學系暨研究所] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	412	检视/开启
N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability.pdf		4880Kb	Adobe PDF	84	检视/开启

在機構典藏中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....