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Science 15 June 2007:
Vol. 316. no. 5831, pp. 1619 - 1622
DOI: 10.1126/science.1137065
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Reports

Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation

Josipa Bilic,1 Ya-Lin Huang,1 Gary Davidson,1 Timo Zimmermann,2 Cristina-Maria Cruciat,1 Mariann Bienz,3 Christof Niehrs1*

Multiple signaling pathways, including Wnt signaling, participate in animal development, stem cell biology, and human cancer. Although many components of the Wnt pathway have been identified, unresolved questions remain as to the mechanism by which Wnt binding to its receptors Frizzled and Low-density lipoprotein receptor–related protein 6 (LRP6) triggers downstream signaling events. With live imaging of vertebrate cells, we show that Wnt treatment quickly induces plasma membrane–associated LRP6 aggregates. LRP6 aggregates are phosphorylated and can be detergent-solubilized as ribosome-sized multiprotein complexes. Phospho-LRP6 aggregates contain Wnt-pathway components but no common vesicular traffic markers except caveolin. The scaffold protein Dishevelled (Dvl) is required for LRP6 phosphorylation and aggregation. We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and ß-catenin stabilization.

1 Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
2 Advanced Light Microscopy Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
3 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.

* To whom correspondence should be addressed. E-mail: Niehrs{at}DKFZ-Heidelberg.DE

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