title: Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila.
abstract: Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP). PCP depends upon Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl). We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment.
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Lindsay K
authors.initials: LK
authors.lastname: Kelly
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Wang A
authors.initials: WA
authors.lastname: Yanfeng
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: marek.mlodzik@mssm.edu.
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology*; D051157:Frizzled Receptors / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; C111638:Vang protein, Drosophila; C113519:dco protein, Drosophila; C058784:fz protein, Drosophila; D048149:Casein Kinase 1 epsilon