Plasma membrane recruitment of dephosphorylated β-catenin upon activation of the Wnt pathway

Jolita Hendriksen, Marnix Jansen, Carolyn M. Brown, Hella van der Velde, Marco van Ham, Niels Galjart, G. Johan Offerhaus, Francois Fagotto, Maarten Fornerod

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1793-1802
Number of pages10
JournalJournal of Cell Science
Volume121
Issue number11
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Keywords

  • β-catenin
  • APC
  • Axin
  • LRP5/6
  • Wnt signaling

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Hendriksen, J., Jansen, M., Brown, C. M., van der Velde, H., van Ham, M., Galjart, N., Offerhaus, G. J., Fagotto, F., & Fornerod, M. (2008). Plasma membrane recruitment of dephosphorylated β-catenin upon activation of the Wnt pathway. Journal of Cell Science, 121(11), 1793-1802. https://doi.org/10.1242/jcs.025536