Interaction of Frizzled 7 and Dishevelled in Xenopus.
Frizzled proteins act as putative Wnt receptors and depending on Wnt/Frizzled interactions distinct intracellular pathways can be activated. The canonical Wnt pathway, triggered by Wnt-1-type ligands, is the best characterized and involves the activation of the cytoplasmic protein Dishevelled (Dsh). The Xenopus frizzled 7 receptor (Xfz7) can act in the canonical (Wnt-1-type) as well as in a non-canonical Wnt pathway which involves the activation of protein kinase C (PKC). In order to analyze the interaction between Xfz7 and Xdsh protein, we tested the effect of overexpression of Xfz7 on the subcellular distribution of Xdsh-myc protein. We demonstrate that Xfz7 can recruit Xdsh-myc to the plasma membrane and target genes of the Wnt-1-type pathway such as siamois and nodal related 3 (Xnr-3) are only activated in the presence of exogenous Xdsh-myc. Xfz7 in combination with Xwnt-8b, however, is able to induce siamois even in the absence of Xdsh-myc. Similar results were obtained after expression of Human frizzled 5 (Hfz5) together with Xwnt-5a but this receptor-ligand combination recruits Xdsh-myc only very poorly to the membrane. These results suggests that the endogenous Xdsh pool and exogenous Xdsh-myc differ in their ability to be recruited by Frizzled receptors.
Medina
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Department of Cell Biology, Max-Planck Institute for Developmental Biology, Tübingen, Germany.
Steinbeisser
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H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D000072261:Dishevelled Proteins; D005455:Fluorescent Antibody Technique; D051157:Frizzled Receptors; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C498589:FZD5 protein, human; C115810:FZD7 protein, human; D051157:Frizzled Receptors; C492040:Fzd7 protein, Xenopus; D018398:Homeodomain Proteins; D008024:Ligands; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; C093133:SIA1 protein, Xenopus; D016212:Transforming Growth Factor beta; C495249:WNT1 protein, Xenopus; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C094620:nodal3.1 protein, Xenopus; D012313:RNA; D011493:Protein Kinase C