Modulation of LRP6-mediated Wnt signaling by molecular chaperone Mesd

Yonghe Li, Wenyan Lu, Xi He, Guojun Bu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

LRP6 is a Wnt coreceptor at the cell surface. Here, we report that a specialized molecular chaperone Mesd modulates LRP6-mediated Wnt signaling and how different LRP6 mutants exhibit differential effects on Wnt signaling. We found that overexpression of increasing amounts of the full-length LRP6 enhances Wnt signaling in a dose dependent manner only in the presence of a co-expression of the molecular chaperone Mesd, which promotes LRP6 folding and maturation to the cell surface. We also demonstrated that LRP6 mutant lacking the intracellular domain impedes LRP6 cell surface expression and Wnt signaling in a dominant-negative fashion by sequestering Mesd from promoting LRP6 folding. Our results present novel mechanisms by which Mesd and LRP6 modulate Wnt signaling.

Original languageEnglish (US)
Pages (from-to)5423-5428
Number of pages6
JournalFEBS Letters
Volume580
Issue number22
DOIs
StatePublished - Oct 2 2006

Keywords

  • Chaperone
  • LRP6
  • Mesd
  • Wnt signaling

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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