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The Postsynaptic Density 95/Disc-Large/Zona Occludens Protein Syntenin Directly Interacts with Frizzled 7 and Supports Noncanonical Wnt Signaling

Authors :
Eva Mortier
Kathleen Lambaerts
Vincent Taelman
Gisèle Degeest
Annouck Luyten
Pascale Zimmermann
Claude Van Campenhout
Guido David
Gunther Wuytens
Eric Bellefroid
Source :
Molecular Biology of the Cell. 19:1594-1604
Publication Year :
2008
Publisher :
American Society for Cell Biology (ASCB), 2008.

Abstract

Wnt signaling pathways are essential for embryonic patterning, and they 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 postsynaptic density 95/disc-large/zona occludens (PDZ) protein syntenin binds to syndecans, Wnt coreceptors, and known stimulators of protein kinase C (PKC)α 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 PKCα/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 that it might function as a direct intracellular link between Frizzled and syndecans.

Details

ISSN :
19394586 and 10591524
Volume :
19
Database :
OpenAIRE
Journal :
Molecular Biology of the Cell
Accession number :
edsair.doi.dedup.....b84f84d5ad4e3f885a3544c65bf8c31a