title: Distinct functionality of dishevelled isoforms on Ca2+/calmodulin-dependent protein kinase 2 (CamKII) in Xenopus gastrulation.
abstract: Wnt ligands trigger the activation of a variety of β-catenin-dependent and β-catenin-independent intracellular signaling cascades. Despite the variations in intracellular signaling, Wnt pathways share the effector proteins frizzled, dishevelled, and β-arrestin. It is unclear how the specific activation of individual branches and the integration of multiple signals are achieved. We hypothesized that the composition of dishevelled-β-arrestin protein complexes contributes to signal specificity and identified CamKII as an interaction partner of the dishevelled-β-arrestin protein complex by quantitative functional proteomics. Specifically, we found that CamKII isoforms interact differentially with the three vertebrate dishevelled proteins. Dvl1 is required for the activation of CamKII and PKC in the Wnt/Ca(2+) pathway. However, CamKII interacts with Dvl2 but not with Dvl1, and Dvl2 is necessary to mediate CamKII function downstream of Dvl1 in convergent extension movements in Xenopus gastrulation. Our findings indicate that the different Dvl proteins and the composition of dishevelled-β-arrestin protein complexes contribute to the specific activation of individual branches of Wnt signaling.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Gentzel
authors.affiliation: Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Schille
authors.affiliation: Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Rauschenberger
authors.affiliation: Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schambony
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D000072261:Dishevelled Proteins; D054262:Gastrulation; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis; D000071557:beta-Arrestins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019390:Arrestins; C000606586:DVL1 protein, Xenopus; C000606578:DVL1 protein, human; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D029867:Xenopus Proteins; D000071557:beta-Arrestins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2