C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells

Miho Fujiwara, Shintaro Kato, Yuki Niwa, Takehiro Suzuki, Miyu Tsuchiya, Yukiko Sasazawa, Naoshi Dohmae, Siro Simizu

Research output: Contribution to journalLetter

16 Citations (Scopus)

Abstract

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 Trp153 and Trp156; however, it had been unclear whether these sites are C-mannosylated or not. We demonstrated that Rspo3 was C-mannosylated at both Trp153 and Trp156 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.

Original languageEnglish
Pages (from-to)2639-2649
Number of pages11
JournalFEBS Letters
DOIs
Publication statusPublished - 2016 Aug 1

Keywords

  • C-mannosylation
  • glycobiology
  • mass spectrometry
  • R-spondin3
  • signal transduction
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Medicine(all)
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells'. Together they form a unique fingerprint.

  • Cite this