β-Arrestin interacts with the beta/gamma subunits of trimeric G-proteins and dishevelled in the Wnt/Ca(2+) pathway in xenopus gastrulation

PLoS One. 2014 Jan 29;9(1):e87132. doi: 10.1371/journal.pone.0087132. eCollection 2014.

Abstract

β-Catenin independent, non-canonical Wnt signaling pathways play a major role in the regulation of morphogenetic movements in vertebrates. The term non-canonical Wnt signaling comprises multiple, intracellularly divergent, Wnt-activated and β-Catenin independent signaling cascades including the Wnt/Planar Cell Polarity and the Wnt/Ca(2+) cascades. Wnt/Planar Cell Polarity and Wnt/Ca(2+) pathways share common effector proteins, including the Wnt ligand, Frizzled receptors and Dishevelled, with each other and with additional branches of Wnt signaling. Along with the aforementioned proteins, β-Arrestin has been identified as an essential effector protein in the Wnt/β-Catenin and the Wnt/Planar Cell Polarity pathway. Our results demonstrate that β-Arrestin is required in the Wnt/Ca(2+) signaling cascade upstream of Protein Kinase C (PKC) and Ca(2+)/Calmodulin-dependent Protein Kinase II (CamKII). We have further characterized the role of β-Arrestin in this branch of non-canonical Wnt signaling by knock-down and rescue experiments in Xenopus embryo explants and analyzed protein-protein interactions in 293T cells. Functional interaction of β-Arrestin, the β subunit of trimeric G-proteins and Dishevelled is required to induce PKC activation and membrane translocation. In Xenopus gastrulation, β-Arrestin function in Wnt/Ca(2+) signaling is essential for convergent extension movements. We further show that β-Arrestin physically interacts with the β subunit of trimeric G-proteins and Dishevelled, and that the interaction between β-Arrestin and Dishevelled is promoted by the beta/gamma subunits of trimeric G-proteins, indicating the formation of a multiprotein signaling complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Arrestins / metabolism*
  • Calcium Signaling
  • Dishevelled Proteins
  • Embryo, Nonmammalian / metabolism
  • Enzyme Activation
  • Gastrulation*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Kinase C-alpha / metabolism
  • Protein Subunits / metabolism
  • Protein Transport
  • Wnt Signaling Pathway
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism
  • beta-Arrestins

Substances

  • Adaptor Proteins, Signal Transducing
  • Arrestins
  • Dishevelled Proteins
  • Phosphoproteins
  • Protein Subunits
  • beta-Arrestins
  • Protein Kinase C-alpha
  • Heterotrimeric GTP-Binding Proteins

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft (SCHA965/6-1 to A.S., www.dfg.de), the Max-Planck-Society (to M.G., www.mpg.de) and by Czech Science Foundation (204/09/0498, 204/09/J030 to V.B., www.gacr.cz) and EMBO Installation Grant, the Ministry of Education Youth and Sport of the Czech Republic (MSM0021622430 to V.B., www.embo.org). In addition, the authors acknowledge support by Deutsche Forschungsgemeinschaft (www.dfg.de) and Friedrich-Alexander-Universität Erlangen-Nürnberg (www.fau.de) within the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.