title: Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila.
abstract: Members of the casein kinase I (CKI) family have been implicated in regulating canonical Wnt/Wingless (Wg) signaling by phosphorylating multiple pathway components. Overexpression of CKI in vertebrate embryos activates Wg signaling, and one target is thought to be the cytoplasmic effector Dishevelled (Dsh), which is an in vitro target of CKI phosphorylation. Phosphorylation of Dsh by CKI has also been suggested to switch its activity from noncanonical to canonical Wingless signaling. However, in vivo loss-of-function experiments have failed to identify a clear role for CKI in positive regulation of Wg signaling. By examining hypomorphic mutations of the Drosophila CKIepsilon homolog discs overgrown (dco)/double-time, we now show that it is an essential component of the noncanonical/planar cell polarity pathway. Genetic interactions indicate that dco acts positively in planar polarity signaling, demonstrating that it does not act as a switch between canonical and noncanonical pathways. Mutations in dco result in a reduced level of Dishevelled phosphorylation in vivo. Furthermore, in these mutants, Dishevelled fails to adopt its characteristic asymmetric subcellular localisation at the distal end of pupal wing cells, and the site of hair outgrowth is disrupted. Finally, we also find that dco function in polarity is partially redundant with CKIalpha.
authors.affiliation: Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Strutt
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Price
authors.forename: David
authors.initials: D
authors.lastname: Strutt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D048149:Casein Kinase 1 epsilon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048128:Casein Kinase Ialpha / Q000502:physiology; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051157:Frizzled Receptors / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism; D051155:Wnt1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D051155:Wnt1 Protein; C113519:dco protein, Drosophila; C000606588:dsh protein, Drosophila; C058784:fz protein, Drosophila; C074622:wg protein, Drosophila; D048149:Casein Kinase 1 epsilon; D048128:Casein Kinase Ialpha