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

FEBS Lett. 2016 Aug;590(16):2639-49. doi: 10.1002/1873-3468.12274. Epub 2016 Jul 13.

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 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.

Keywords: C-mannosylation; R-spondin3; Wnt/β-catenin signaling; glycobiology; mass spectrometry; signal transduction.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental
  • Glycosylation
  • Homeostasis / genetics
  • Humans
  • Mannose / metabolism
  • Mutant Proteins / biosynthesis*
  • Mutant Proteins / genetics
  • Thrombospondins / biosynthesis*
  • Thrombospondins / genetics
  • Thrombospondins / metabolism
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Mutant Proteins
  • RSPO3 protein, human
  • Thrombospondins
  • beta Catenin
  • Mannose