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Mol Biol Cell 2015 Mar 01;265:966-77. doi: 10.1091/mbc.E14-06-1089.
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Distinct functionality of dishevelled isoforms on Ca2+/calmodulin-dependent protein kinase 2 (CamKII) in Xenopus gastrulation.

Gentzel M , Schille C , Rauschenberger V , Schambony A .

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.

PubMed ID: 25568338
PMC ID: PMC4342031
Article link: Mol Biol Cell

Species referenced: Xenopus laevis
Genes referenced: arrb2 camk2g ctnnb1 dvl1 dvl2 dvl3 fzd7 myc
Morpholinos: dvl1 MO1 dvl2 MO1 dvl3 MO1 dvl3 MO2

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References [+] :
Bastock, Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. 2003, Pubmed