C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells
C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells
复制标题
DOI：
10.1002/1873-3468.12274
复制
发表时间：
2016-08-01
期刊：
影响因子：
3.5
通讯作者：
Simizu, Siro
中科院分区：
文献类型：
--
作者：
Fujiwara, Miho;Kato, Shintaro;Simizu, Siro
R-spondin 3（Rspo 3）是一种分泌性蛋白，其作为经典Wnt/β-catenin信号传导的激动剂，在胚胎发育和稳态中起重要作用。在这项研究中，我们专注于C-甘露糖基化，一种独特类型的糖基化，人Rspo 3。Rspo 3在Trp（153）和Trp（156）处具有两个推定的C-甘露糖基化位点;然而，尚不清楚这些位点是否被C-甘露糖基化。我们通过质谱证明Rspo 3在Trp（153）和Trp（156）处都被C-甘露糖基化。使用C-甘露糖基化缺陷的Rspo 3 music过表达细胞系，我们发现Rspo 3的C-甘露糖基化促进其分泌并激活Wnt/β-连环蛋白信号传导。
R-spondin3 (Rspo3) is a secreted protein, which acts as an agonist of canonical Wnt/beta-catenin signaling that plays an important role in embryonic development and homeostasis. In this study, we focused on C-mannosylation, a unique type of glycosylation, of human Rspo3. Rspo3 has two putative C-mannosylation sites at Trp(153) and Trp(156); however, it had been unclear whether these sites are C-mannosylated or not. We demonstrated that Rspo3 was C-mannosylated at both Trp(153) and Trp(156) by mass spectrometry. Using C-mannosylation-defective Rspo3 mutant-overexpressing cell lines, we found that C-mannosylation of Rspo3 promotes its secretion and activates Wnt/beta-catenin signaling.