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First published online 6 May 2008
doi: 10.1242/jcs.025536

Journal of Cell Science 121, 1793-1802 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Jolita Hendriksen1,*, Marnix Jansen1,2,*,{ddagger}, Carolyn M. Brown3, Hella van der Velde1, Marco van Ham4, Niels Galjart4, G. Johan Offerhaus2, Francois Fagotto3 and Maarten Fornerod1,§

1 Department of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
2 Department of Pathology, University Medical Center Utrecht, 3584 ZX Utrecht, The Netherlands
3 Department of Biology, McGill University,1205 Dr Penfield Avenue, Montreal, QC H3A 1B1, Canada
4 Department of Cell Biology, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

§ Author for correspondence (e-mail: m.fornerod{at}nki.nl)

Accepted 7 March 2008

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.

Key words: Wnt signaling, β-catenin, APC, Axin, LRP5/6


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β-catenin: to the membrane and back

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C. S. Cselenyi, K. K. Jernigan, E. Tahinci, C. A. Thorne, L. A. Lee, and E. Lee
LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of {beta}-catenin
PNAS, June 10, 2008; 105(23): 8032 - 8037.
[Abstract] [Full Text] [PDF]


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