Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding.
Epithelial planar cell polarity (PCP) is evident in the cellular organization of many tissues in vertebrates and invertebrates. In mammals, PCP signalling governs convergent extension during gastrulation and the organization of a wide variety of structures, including the orientation of body hair and sensory hair cells of the inner ear. In Drosophila melanogaster, PCP is manifest in adult tissues, including ommatidial arrangement in the compound eye and hair orientation in wing cells. PCP establishment requires the conserved Frizzled/Dishevelled PCP pathway. Mutations in PCP-pathway-associated genes cause aberrant orientation of body hair or inner-ear sensory cells in mice, or misorientation of ommatidia and wing hair in D. melanogaster. Here we provide mechanistic insight into Frizzled/Dishevelled signalling regulation. We show that the ankyrin-repeat protein Diego binds directly to Dishevelled and promotes Frizzled signalling. Dishevelled can also be bound by the Frizzled PCP antagonist Prickle. Strikingly, Diego and Prickle compete with one another for Dishevelled binding, thereby modulating Frizzled/Dishevelled activity and ensuring tight control over Frizzled PCP signalling.
Jenny
Andreas
A
Mount Sinai School of Medicine, Brookdale Department of Molecular, Cellular and Developmental Biology, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Reynolds-Kenneally
Jessica
J
Das
Gishnu
G
Burnett
Micheal
M
Mlodzik
Marek
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C492998:Dgo protein, Drosophila; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D051157:Frizzled Receptors; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; C111638:Vang protein, Drosophila; C064196:dpp protein, Drosophila; C000606588:dsh protein, Drosophila; C058784:fz protein, Drosophila; C121600:pk protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila