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The Postsynaptic Density 95/Disc-Large/Zona Occludens Protein Syntenin Directly Interacts with Frizzled 7 and Supports Noncanonical Wnt Signaling
- 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.
- Subjects :
- Frizzled
DNA, Complementary
Syndecans
Proto-Oncogene Proteins c-jun
Syntenins
Molecular Sequence Data
PDZ domain
Xenopus Proteins
Biology
Models, Biological
Receptors, G-Protein-Coupled
Xenopus laevis
Animals
Humans
Amino Acid Sequence
Phosphorylation
Molecular Biology
Cells, Cultured
chemistry.chemical_classification
Binding Sites
Base Sequence
Sequence Homology, Amino Acid
Convergent extension
Wnt signaling pathway
Gene Expression Regulation, Developmental
LRP6
LRP5
Articles
Cell Biology
Surface Plasmon Resonance
Frizzled Receptors
Recombinant Proteins
Protein Structure, Tertiary
Cell biology
Dishevelled
Wnt Proteins
STAT1 Transcription Factor
chemistry
Mutagenesis, Site-Directed
Female
Postsynaptic density
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....b84f84d5ad4e3f885a3544c65bf8c31a