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Modulation of LRP6‐mediated Wnt signaling by molecular chaperone Mesd
Author(s) -
Li Yonghe,
Lu Wenyan,
He Xi,
Bu Guojun
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.011
Subject(s) - lrp6 , wnt signaling pathway , modulation (music) , chaperone (clinical) , microbiology and biotechnology , chemistry , signal transduction , biochemistry , biology , medicine , physics , pathology , acoustics
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.