beta-Arrestin Interacts with the Beta/Gamma Subunits of Trimeric G-Proteins and Dishevelled in the Wnt/Ca2+ Pathway in Xenopus Gastrulation

Published: PLOS ONE 9 Authors: Seitz, K., Dursch, V., Harnos, J., Bryja, V., Gentzel, M., Schambony, A. Year: 2014

Abstract

beta-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 beta-Catenin independent signaling cascades including the Wnt/Planar Cell Polarity and the Wnt/Ca2+ cascades. Wnt/Planar Cell Polarity and Wnt/Ca2+ 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, beta-Arrestin has been identified as an essential effector protein in the Wnt/beta-Catenin and the Wnt/Planar Cell Polarity pathway. Our results demonstrate that beta-Arrestin is required in the Wnt/Ca2+ signaling cascade upstream of Protein Kinase C (PKC) and Ca2+/Calmodulin-dependent Protein Kinase II (CamKII). We have further characterized the role of beta-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 beta-Arrestin, the beta subunit of trimeric G-proteins and Dishevelled is required to induce PKC activation and membrane translocation. In Xenopus gastrulation, beta-Arrestin function in Wnt/Ca2+ signaling is essential for convergent extension movements. We further show that beta-Arrestin physically interacts with the beta subunit of trimeric G-proteins and Dishevelled, and that the interaction between beta-Arrestin and Dishevelled is promoted by the beta/gamma subunits of trimeric G-proteins, indicating the formation of a multiprotein signaling complex.