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PMID:18256285

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Citation

Luyten, A, Mortier, E, Van Campenhout, C, Taelman, V, Degeest, G, Wuytens, G, Lambaerts, K, David, G, Bellefroid, EJ and Zimmermann, P (2008) The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling. Mol. Biol. Cell 19:1594-604

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.

Links

PubMed PMC2291413 Online version:10.1091/mbc.E07-08-0832

Keywords

Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Cells, Cultured; DNA, Complementary/genetics; Female; Frizzled Receptors/chemistry; Frizzled Receptors/genetics; Frizzled Receptors/metabolism; Gene Expression Regulation, Developmental; Humans; Models, Biological; Molecular Sequence Data; Mutagenesis, Site-Directed; Phosphorylation; Protein Structure, Tertiary; Proto-Oncogene Proteins c-jun/metabolism; Receptors, G-Protein-Coupled/chemistry; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; STAT1 Transcription Factor; Sequence Homology, Amino Acid; Surface Plasmon Resonance; Syndecans/genetics; Syndecans/metabolism; Syntenins/chemistry; Syntenins/genetics; Syntenins/metabolism; Wnt Proteins/metabolism; Xenopus Proteins/chemistry; Xenopus Proteins/genetics; Xenopus Proteins/metabolism; Xenopus laevis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SDCB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75084

F

Seeded From UniProt

complete

HUMAN:SDCB1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SDCB1

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NPG1

F

Seeded From UniProt

complete

HUMAN:SDCB1

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H461

F

Seeded From UniProt

complete

HUMAN:SDCB1

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75084

F

Seeded From UniProt

complete

HUMAN:SDCB1

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SDCB1

enables

GO:0045545: syndecan binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P34741

F

Seeded From UniProt

complete

HUMAN:SDCB1

involved_in

GO:0046330: positive regulation of JNK cascade

ECO:0000305: curator inference used in manual assertion

GO:0042327

P

Seeded From UniProt

complete

HUMAN:SDCB1

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00560

F

Seeded From UniProt

complete

HUMAN:FZD7

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00560

F

Seeded From UniProt

complete

HUMAN:FZD7

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FZD7

involved_in

GO:0046330: positive regulation of JNK cascade

ECO:0000305: curator inference used in manual assertion

GO:0042327

P

Seeded From UniProt

complete

HUMAN:FZD7

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SDC2

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00560

F

Seeded From UniProt

complete

HUMAN:FZD3

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00560

F

Seeded From UniProt

complete

HUMAN:FZD8

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00560

F

Seeded From UniProt

complete


See also

References

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