Title: The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling
Authors: Luyten, Annouck
Mortier, Eva
Van Campenhout, Claude
Taelman, Vincent
Degeest, Gisèle
Wuytens, Gunther
Lambaerts, Kathleen
David, Guido
Bellefroid, Eric J
Zimmermann, Pascale # ×
Issue Date: Apr-2008
Publisher: American Society for Cell Biology
Series Title: Molecular Biology of the Cell vol:19 issue:4 pages:1594-1604
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)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.
ISSN: 1059-1524
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Molecular Genetics Section (-)
Laboratory for Signal Integration in Cell Fate Decision
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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