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

13 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

Fingerprint

Catenins
Glycosylation
Embryonic Development
Mass spectrometry
Mass Spectrometry
Homeostasis
Cells
Cell Line
Proteins

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

Cite this

C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells. / Fujiwara, Miho; Kato, Shintaro; Niwa, Yuki; Suzuki, Takehiro; Tsuchiya, Miyu; Sasazawa, Yukiko; Dohmae, Naoshi; Simizu, Siro.

In: FEBS Letters, 01.08.2016, p. 2639-2649.

Research output: Contribution to journalLetter

Fujiwara, Miho ; Kato, Shintaro ; Niwa, Yuki ; Suzuki, Takehiro ; Tsuchiya, Miyu ; Sasazawa, Yukiko ; Dohmae, Naoshi ; Simizu, Siro. / C-mannosylation of R-spondin3 regulates its secretion and activity of Wnt/β-catenin signaling in cells. In: FEBS Letters. 2016 ; pp. 2639-2649.
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AU - Fujiwara, Miho

AU - Kato, Shintaro

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AU - Suzuki, Takehiro

AU - Tsuchiya, Miyu

AU - Sasazawa, Yukiko

AU - Dohmae, Naoshi

AU - Simizu, Siro

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