Modulation of LRP6-mediated Wnt signaling by molecular chaperone Mesd

FEBS Lett. 2006 Oct 2;580(22):5423-8. doi: 10.1016/j.febslet.2006.09.011. Epub 2006 Sep 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Gene Expression
  • Humans
  • LDL-Receptor Related Proteins / genetics
  • LDL-Receptor Related Proteins / metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Folding*
  • Signal Transduction* / genetics
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*


  • LDL-Receptor Related Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • MESD protein, human
  • Molecular Chaperones
  • Wnt Proteins