β-Arrestin interacts with the beta/gamma subunits of trimeric G-proteins and dishevelled in the Wnt/Ca(2+) pathway in xenopus gastrulation.
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.
Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Katharina
K
Seitz
Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Verena
V
Dürsch
Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Jakub
J
Harnoš
Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic ; Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Vitezslav
V
Bryja
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Marc
M
Gentzel
Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Alexandra
A
Schambony
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D020013:Calcium Signaling; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004789:Enzyme Activation; D054262:Gastrulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D060449:Wnt Signaling Pathway; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism; D000071557:beta-Arrestins
D048868:Adaptor Proteins, Signal Transducing; D019390:Arrestins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D000071557:beta-Arrestins; D051571:Protein Kinase C-alpha; D020962:Heterotrimeric GTP-Binding Proteins