Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila

• Published in: Cell reports (Cambridge) Vol. 16; no. 2; pp. 344 - 356
• Main Authors: Kelly, Lindsay K., Wu, Jun, Yanfeng, Wang A., Mlodzik, Marek
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.07.2016; Elsevier
• Subjects: Animals; Casein Kinase Iepsilon - physiology; Cell Membrane - metabolism; Cell Polarity; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - enzymology; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Frizzled Receptors - physiology; Membrane Proteins - metabolism; Phosphorylation; Protein Processing, Post-Translational; Protein Transport
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.06.010

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. [Display omitted] •Fz induces Vang phosphorylation in a cell-autonomous but Dsh-independent manner•CK1ε/Dco mediates Vang phosphorylation on conserved N-terminal serine residues•Phosphorylation is critical for polarized localization and function of Vang in PCP Kelly et al. find that Vang phosphorylation is involved in planar cell polarity (PCP) signaling. This phosphorylation is mediated by CK1ε/Dco and requires cell-autonomous Frizzled signaling activity but is independent of Dsh function. Vang phosphorylation is essential for polarized membrane localization and Vang function in PCP.