N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability
學年 104
學期 2
出版（發表）日期 2016-06-27
作品名稱 N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability
作品名稱（其他語言）
著者 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
單位
出版者
著錄名稱、卷期、頁數 International Journal of Molecular Sciences 17(6), pp.937
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.
關鍵字 R-spondin 1; N-glycosylation;secretion;stability;Wnt signaling
語言 en
ISSN 1422-0067
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Tsai, Jen-Ning
審稿制度 是
國別 CHE
公開徵稿
出版型式 ,電子版
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機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/107112 )