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C ‐mannosylation of R‐spondin3 regulates its secretion and activity of Wnt/β‐catenin signaling in cells
Author(s) -
Fujiwara Miho,
Kato Shintaro,
Niwa Yuki,
Suzuki Takehiro,
Tsuchiya Miyu,
Sasazawa Yukiko,
Dohmae Naoshi,
Simizu Siro
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12274
Subject(s) - wnt signaling pathway , secretion , glycosylation , mutant , catenin , chemistry , microbiology and biotechnology , signal transduction , biology , biochemistry , gene
R‐spondin3 (Rspo3) is a secreted protein, which acts as an agonist of canonical Wnt/β‐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/β‐catenin signaling.