QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

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

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.025536v1 121/11/1793    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hendriksen, J. Articles by Fornerod, M. Search for Related Content PubMed PubMed Citation Articles by Hendriksen, J. Articles by Fornerod, M. Social Bookmarking                         What's this?

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

Jolita Hendriksen^1,*, Marnix Jansen^1,2,*,, Carolyn M. Brown³, Hella van der Velde¹, Marco van Ham⁴, Niels Galjart⁴, G. Johan Offerhaus², Francois Fagotto³ and Maarten Fornerod^1,

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

β-catenin: to the membrane and back

JCS 2008 121: 1103. [Full Text]  

This article has been cited by other articles:

				K. M. Cadigan and M. Peifer Wnt Signaling from Development to Disease: Insights from Model Systems Cold Spring Harb Perspect Biol, August 1, 2009; 1(2): a002881 - a002881. [Abstract] [Full Text] [PDF]

				H.-S. Kwon, H.-S. Lee, Y. Ji, J. S. Rubin, and S. I. Tomarev Myocilin Is a Modulator of Wnt Signaling Mol. Cell. Biol., April 15, 2009; 29(8): 2139 - 2154. [Abstract] [Full Text] [PDF]

				H.-X. Wang, F. R. Tekpetey, and G. M. Kidder Identification of WNT/{beta}-CATENIN signaling pathway components in human cumulus cells Mol. Hum. Reprod., January 1, 2009; 15(1): 11 - 17. [Abstract] [Full Text] [PDF]

				O. Sokolova, P. M. Bozko, and M. Naumann Helicobacter pylori Suppresses Glycogen Synthase Kinase 3{beta} to Promote {beta}-Catenin Activity J. Biol. Chem., October 24, 2008; 283(43): 29367 - 29374. [Abstract] [Full Text] [PDF]

				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]