Prickle Mediates Feedback Amplification to Generate Asymmetric Planar Cell Polarity Signaling

• Published in: Cell Vol. 109; no. 3; pp. 371 - 381
• Main Authors: Tree, David R.P., Shulman, Joshua M., Rousset, Raphaël, Scott, Matthew P., Gubb, David, Axelrod, Jeffrey D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-05-2002
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Cell Polarity - genetics; Cell Polarity - physiology; Cloning, Molecular; Cytoplasm - metabolism; Dishevelled Proteins; DNA-Binding Proteins - metabolism; Drosophila - anatomy & histology; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins; Epistasis, Genetic; Feedback, Physiological - physiology; Frizzled Receptors; Humans; Insect Proteins - genetics; Insect Proteins - metabolism; LIM Domain Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Osteosarcoma - genetics; Osteosarcoma - pathology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Pupa; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, G-Protein-Coupled; Signal Transduction; Tumor Cells, Cultured; Wings, Animal - cytology; Wings, Animal - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00715-8

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.