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Mol Biol Cell 2008 Apr 01;194:1594-604. doi: 10.1091/mbc.e07-08-0832.
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The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.

Luyten A , Mortier E , Van Campenhout C , Taelman V , Degeest G , Wuytens G , Lambaerts K , David G , Bellefroid EJ , Zimmermann P .

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)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 PKCalpha/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.

PubMed ID: 18256285
PMC ID: PMC2291413
Article link: Mol Biol Cell

Species referenced: Xenopus laevis
Genes referenced: actc1 cdc42 dvl1 dvl2 fzd3 fzd7 fzd8 jun myc sdc2 sdc4 sdcbp
Morpholinos: sdcbp MO1 sdcbp MO2

Article Images: [+] show captions
References [+] :
Ataman, Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. 2006, Pubmed