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MBC in Press, published online ahead of print February 6, 2008
Mol. Biol. Cell 10.1091/mbc.E07-08-0832

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Submitted on August 28, 2007
Revised on January 3, 2008
Accepted on January 30, 2008

The PDZ Protein Syntenin Directly Interacts with Frizzled 7 and Supports Non-canonical Wnt Signaling

Annouck Luyten,*{dagger} Eva Mortier,*{dagger} Claude Van Campenhout,{ddagger} Vincent Taelman,{ddagger} Gisèle Degeest,*{dagger} Gunther Wuytens,*{dagger} Kathleen Lambaerts,*{dagger} Guido David,*{dagger} Eric J. Bellefroid,{ddagger} and Pascale Zimmermann*{dagger}

*Department of Human Genetics, K.U.Leuven, B-3000 Leuven, Belgium; {dagger}Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium; {ddagger}Institut de Biologie et de Medecine Moléculaires, Université Libre de Bruxelles, B-6041 Gosselies, Belgium

Monitoring Editor: Carl-Henrik Heldin

Wnt signaling pathways are essential for embryonic patterning and are disturbed in a wide spectrum of diseases, including cancer. An unresolved question is how the different Wnt pathways are supported and regulated. We previously established that the PDZ protein syntenin binds to syndecans, Wnt coreceptors and known stimulators of PKC{alpha} and CDC42 activity. Here, we show that syntenin also interacts with the C-terminal PDZ binding motif of several Frizzled Wnt receptors, without compromising the recruitment of Dishevelled, a key downstream Wnt-signaling component. Syntenin is coexpressed with cognate Frizzled during early development in Xenopus. Overexpression and down-regulation of syntenin disrupt convergent extension movements, supporting a role for syntenin in noncanonical Wnt signaling. Syntenin stimulates c-jun phosphorylation and modulates Frizzled 7 signaling, in particular the PKC{alpha}/CDC42 noncanonical Wnt signaling cascade. The syntenin-Frizzled 7 binding mode indicates syntenin can accommodate Frizzled 7-syndecan complexes. We propose that syntenin is a novel component of the Wnt signal transduction cascade and might function as a direct intracellular link between Frizzled and syndecans.

Address correspondence to: Pascale Zimmermann (pascale.zimmermann{at}med.kuleuven.be)






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