DAnkrd49 and Bdbt act via Casein kinase Iε to regulate planar polarity in Drosophila
Open Access
- 4 August 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 16 (8), e1008820
- https://doi.org/10.1371/journal.pgen.1008820
Abstract
The core planar polarity proteins are essential mediators of tissue morphogenesis, controlling both the polarised production of cellular structures and polarised tissue movements. During development the core proteins promote planar polarisation by becoming asymmetrically localised to opposite cell edges within epithelial tissues, forming intercellular protein complexes that coordinate polarity between adjacent cells. Here we describe a novel protein complex that regulates the asymmetric localisation of the core proteins in the Drosophila pupal wing. DAnkrd49 (an ankyrin repeat protein) and Bride of Doubletime (Bdbt, a non-canonical FK506 binding protein family member) physically interact, and regulate each other’s levels in vivo. Loss of either protein results in a reduction in core protein asymmetry and disruption of the placement of trichomes at the distal edge of pupal wing cells. Post-translational modifications are thought to be important for the regulation of core protein behaviour and their sorting to opposite cell edges. Consistent with this, we find that loss of DAnkrd49 or Bdbt leads to reduced phosphorylation of the core protein Dishevelled and to decreased Dishevelled levels both at cell junctions and in the cytoplasm. Bdbt has previously been shown to regulate activity of the kinase Discs Overgrown (Dco, also known as Doubletime or Casein Kinase Iε), and Dco itself has been implicated in regulating planar polarity by phosphorylating Dsh as well as the core protein Strabismus. We demonstrate that DAnkrd49 and Bdbt act as dominant suppressors of Dco activity. These findings support a model whereby Bdbt and DAnkrd49 act together to modulate the activity of Dco during planar polarity establishment. In many animal tissues, sheets of cells are polarised in the plane of the tissue, which is evident by the production of polarised structures, such as hairs on the fly wing that point in the same direction or cilia that beat in the same direction. One group of proteins controlling this coordinated polarity are the core planar polarity proteins, which localise asymmetrically within cells such that some core proteins localise to one cell end and others to the opposite cell end. It is thought that modifications such as phosphorylation may locally regulate core protein stability, and this promotes sorting of proteins to different cell ends. We identify two proteins, DAnkrd49 and Bdbt, that form a complex and regulate core protein asymmetry. Loss of either protein causes a reduction in overall levels of the core protein Dishevelled (Dsh), and a reduction in its phosphorylation. We provide evidence that the effect on core protein asymmetry is mediated via regulation of the kinase activity of Discs overgrown (Dco, also known as Doubletime/Casein Kinase Iε) by DAnkrd49 and Bdbt. We propose that modulation of Dco activity by DAnkrd49 and Bdbt is a key step in the sorting of core proteins to opposite cell ends.Funding Information
- Wellcome Trust (084469/Z/07/Z, 100986/Z/13/Z, 210630/Z/18/Z)
This publication has 67 references indexed in Scilit:
- A Protein Complex Network of Drosophila melanogasterCell, 2011
- Principles of planar polarity in animal developmentDevelopment, 2011
- Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing Vangl2 Phosphorylation through Ror2Developmental Cell, 2011
- Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylationJournal of Bone and Joint Surgery, 2010
- Cell Flow Reorients the Axis of Planar Polarity in the Wing Epithelium of DrosophilaCell, 2010
- Processing and phosphorylation of the Fat receptorProceedings of the National Academy of Sciences of the United States of America, 2009
- Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs OvergrownCurrent Biology, 2009
- The planar polarity pathway promotes coordinated cell migration duringDrosophilaoogenesisDevelopment, 2007
- The Drosophila casein kinase Iε/δ Discs overgrown promotes cell survival via activation of DIAP1 expressionDevelopmental Biology, 2007
- Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: A computer modelDevelopmental Dynamics, 2005