The standard model of Wnt signaling specifies that after receipt of a Wnt ligand at the membranous receptor complex, downstream mediators inhibit a cytoplasmic destruction complex, allowing β-catenin to accumulate in the cytosol and nucleus and co-activate Wnt target genes. Unexpectedly, shortly after Wnt treatment, we detected the dephosphorylated form of β-catenin at the plasma membrane, where it displayed a discontinuous punctate labeling. This pool of β-catenin could only be detected in E-cadherin-/-cells, because in E-cadherin+/+cells Wnt-induced, membranous β-catenin was concealed by a constitutive junctional pool. Wnt-signaling-dependent dephosphorylated β-catenin colocalized at the plasma membrane with two members of the destruction complex - APC and axin - and the activated Wnt co-receptor LRP6. β-catenin induced through the Wnt receptor complex was significantly more competent transcriptionally than overexpressed β-catenin, both in cultured cells and in early Xenopus embryos. Our data reveal a new step in the processing of the Wnt signal and suggest regulation of signaling output beyond the level of protein accumulation.

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Keywords APC, Axin, LRP5/6, Wnt signaling, β-catenin
Persistent URL dx.doi.org/10.1242/jcs.025536, hdl.handle.net/1765/28741
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Citation
Hendriksen, J., Jansen, M., Brown, C.M., van der Velde, H., van Ham, M., Galjart, N.J., … Fornerod, M.W.J.. (2008). Plasma membrane recruitment of dephosphorylated β-catenin upon activation of the Wnt pathway. Journal of Cell Science, 121(11), 1793–1802. doi:10.1242/jcs.025536