Functional analysis of the Xenopus frizzled 7 protein domains using chimeric receptors.
Seven-transmembrane receptors of the frizzled family can interact with secreted Wnt ligands and transmit Wnt signals into the cell. Dependent on the ligand receptor combination, distinct Wnt pathways are activated. Xenopus frizzled 7 (Xfz7) and Xwnt-8b as well as Human frizzled 5 (Hfz5) and Xwnt-5a can act synergistically in the activation of Wnt/beta-catenin target genes siamois (Xsia) and nodal related 3 (Xnr3) and in the induction of ectopic axes in Xenopus embryos. In order to characterize the role of different protein domains of Xfz7 in Wnt/beta-catenin signaling, chimeric Xfz7/Hfz5 receptors were generated in which the extracellular (N5-TC7) or the intracellular domains (NT7-C5) between Xfz7 and Hfz5 were exchanged. We present evidence that the extracellular domain of Xfz7 can interact with Xwnt-5a and that the intracellular C-terminus can transmit a Wnt/beta-catenin signal. Despite these abilities, Xfz7 and Xwnt-5a do not act synergistically in the activation of Wnt/beta-catenin targets. This implies that the interaction of a frizzled receptor with different ligands can result in distinct cellular responses.
Swain
R K
RK
Department of Cell Biology, Max-Planck Institute for Developmental Biology, Tübingen, Germany.
Medina
A
A
Steinbeisser
H
H
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
D017931:DNA Primers; C115810:FZD7 protein, human; D051157:Frizzled Receptors; C492040:Fzd7 protein, Xenopus; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins