The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling.
The Frizzled (Fz) receptor is required cell autonomously in Wnt/beta-catenin and planar cell polarity (PCP) signaling. In addition to these requirements, Fz acts nonautonomously during PCP establishment: wild-type cells surrounding fz(-) patches reorient toward the fz(-) cells. The molecular mechanism(s) of nonautonomous Fz signaling are unknown. Our in vivo studies identify the extracellular domain (ECD) of Fz, in particular its CRD (cysteine rich domain), as critical for nonautonomous Fz-PCP activity. Importantly, we demonstrate biochemical and physical interactions between the FzECD and the transmembrane protein Van Gogh/Strabismus (Vang/Stbm). We show that this function precedes cell-autonomous interactions and visible asymmetric PCP factor localization. Our data suggest that Vang/Stbm can act as a FzECD receptor, allowing cells to sense Fz activity/levels of their neighbors. Thus, direct Fz-Vang/Stbm interactions represent an intriguing mechanism that may account for the global orientation of cells within the plane of their epithelial field.
Wu
Jun
J
Mount Sinai School of Medicine, Department of Developmental and Regenerative Biology, 1 Gustav L. Levy Place, New York, NY 10029, USA.
Mlodzik
Marek
M
Mount Sinai School of Medicine, Department of Developmental and Regenerative Biology, 1 Gustav L. Levy Place, New York, NY 10029, USA. Electronic address: marek.mlodzik@mssm.edu.
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000166:cytology / Q000502:physiology
D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008024:Ligands; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C111638:Vang protein, Drosophila