The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with Frizzled 7 and supports noncanonical Wnt signaling

作者：Luyten Annouck; Mortier Eva; Van Campenhout Claude; Taelman Vincent; Degeest Gisele; Wuytens Gunther; Lambaerts Kathleen; David Guido; Bellefroid Eric J; Zimmermann Pascale^*

来源：Molecular Biology of the Cell, 2008, 19(4): 1594-1604.

DOI：10.1091/mbc.E07-08-0832

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 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 that it might function as a direct intracellular link between Frizzled and syndecans.

• 出版日期2008-4