title: Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling.
abstract: Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle. From initial, symmetric subcellular distributions in pupal wing cells, Frizzled and Dishevelled become highly enriched at the distal portion of the cell cortex. We describe a Prickle-dependent intercellular feedback loop that generates asymmetric Frizzled and Dishevelled localization. In the absence of Prickle, Frizzled and Dishevelled remain symmetrically distributed. Prickle localizes to the proximal side of pupal wing cells and binds the Dishevelled DEP domain, inhibiting Dishevelled membrane localization and antagonizing Frizzled accumulation. This activity is linked to Frizzled activity on the adjacent cell surface. Prickle therefore functions in a feedback loop that amplifies differences between Frizzled levels on adjacent cell surfaces.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, CA 94305, USA.
authors.forename: David R P
authors.initials: DR
authors.lastname: Tree
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Shulman
authors.forename: Raphaël
authors.initials: R
authors.lastname: Rousset
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Scott
authors.forename: David
authors.initials: D
authors.lastname: Gubb
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Axelrod
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004843:Epistasis, Genetic; D025461:Feedback, Physiological / Q000502:physiology*; D051157:Frizzled Receptors; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011679:Pupa; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D019476:Insect Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C000606588:dsh protein, Drosophila; C058784:fz protein, Drosophila; C121600:pk protein, Drosophila