title: Nemo kinase phosphorylates β-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-β-catenin.
abstract: Frizzled planar cell polarity (PCP) signaling regulates cell motility in several tissues, including ommatidial rotation in Drosophila melanogaster. The Nemo kinase (Nlk in vertebrates) has also been linked to cell-motility regulation and ommatidial rotation but its mechanistic role(s) during rotation remain obscure. We show that nemo functions throughout the entire rotation movement, increasing the rotation rate. Genetic and molecular studies indicate that Nemo binds both the core PCP factor complex of Strabismus-Prickle, as well as the E-cadherin-β-catenin (E-cadherin-Armadillo in Drosophila) complex. These two complexes colocalize and, like Nemo, also promote rotation. Strabismus (also called Vang) binds and stabilizes Nemo asymmetrically within the ommatidial precluster; Nemo and β-catenin then act synergistically to promote rotation, which is mediated in vivo by Nemo's phosphorylation of β-catenin. Our data suggest that Nemo serves as a conserved molecular link between core PCP factors and E-cadherin-β-catenin complexes, promoting cell motility.
authors.affiliation: Department of Developmental & Regenerative Biology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkovic
authors.forename: William J
authors.initials: WJ
authors.lastname: Gault
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahnama
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenny
authors.forename: Konstantin
authors.initials: K
authors.lastname: Gaengel
authors.forename: Darrell
authors.initials: D
authors.lastname: Bessette
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Gottardi
authors.forename: Esther M
authors.initials: EM
authors.lastname: Verheyen
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009799:Ocular Physiological Phenomena; D010766:Phosphorylation; D011485:Protein Binding; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C111638:Vang protein, Drosophila; D051176:beta Catenin; C121600:pk protein, Drosophila; C501889:shg protein, Drosophila; D020928:Mitogen-Activated Protein Kinases; C110707:nmo protein, Drosophila