Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity
| Autor: | Ping Helen Chen, Jean-Luc Parent, Kristen Radde-Gallwitz, Shuangding Li, Dongdong Ren, Robert Esterberg, A. Fritz, Véronik Lachance, Fanglu Chi |
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| Rok vydání: | 2011 |
| Předmět: |
Frizzled
Receptors Cell Surface Receptors for Activated C Kinase Mice Cell polarity Animals Zebrafish Multidisciplinary biology Convergent extension Cell Membrane Gastrulation Wnt signaling pathway Cell Polarity Membrane Proteins LRP6 Gastrula Zebrafish Proteins Biological Sciences biology.organism_classification Protein Structure Tertiary Transport protein Cell biology Wnt Proteins Protein Transport Signal transduction Cell Division Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:2264-2269 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1013170108 |
| Popis: | The vertebrate planar cell polarity (PCP) pathway shares molecular components with the β-catenin–mediated canonical Wnt pathway but acts through membrane complexes containing Vang or Frizzled to orient neighboring cells coordinately. The molecular interactions underlying the action of Vang in PCP signaling and specification, however, are yet to be delineated. Here, we report the identification of Rack1 as an interacting protein of a vertebrate Vang protein, Vangl2. We demonstrate that Rack1 is required in zebrafish for PCP-regulated processes, including oriented cell division, cellular polarization, and convergent extension during gastrulation. We further show that the knockdown of Rack1 affects membrane localization of Vangl2 and that the Vangl2-interacting domain of Rack1 has a dominant-negative effect on Vangl2 localization and gastrulation. Moreover, Rack1 antagonizes canonical Wnt signaling. Together, our data suggest that Rack1 regulates the localization of an essential PCP protein and acts as a molecular switch to promote PCP signaling. |
| Databáze: | OpenAIRE |
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