Binding of APC and dishevelled mediates Wnt5a‐regulated focal adhesion dynamics in migrating cells |
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| Authors: | Shinji Matsumoto Katsumi Fumoto Tetsuji Okamoto Kozo Kaibuchi Akira Kikuchi |
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| Institution: | 1. Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan;2. Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, Netherlands;3. Department of Molecular Oral Medicine and Maxillofacial Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan;4. Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Japan |
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| Abstract: | Wnt5a is a representative ligand that activates the Wnt/β‐catenin‐independent pathway, resulting in the regulation of cell adhesion, migration, and polarity, but its molecular mechanism is poorly understood. This report shows that Dishevelled (Dvl) binds to adenomatous polyposis coli (APC) gene product, and this binding is enhanced by Wnt5a. Dvl was involved in the stabilization of the plus end dynamics of microtubules as well as APC. Frizzled2 (Fz2) was present with Wnt5a at the leading edge of migrating cells and formed a complex with APC through Dvl. Fz2 also interacted with integrins at the leading edge, and Dvl and APC associated with and activated focal adhesion kinase and paxillin. The binding of APC to Dvl enhanced the localization of paxillin to the leading edge and was involved in Wnt5a‐dependent focal adhesion turnover. Furthermore, this new Wnt5a signalling pathway was important for the epithelial morphogenesis in the three‐dimensional culture. These results suggest that the functional and physical interaction of Dvl and APC is involved in Wnt5a/Fz2‐dependent focal adhesion dynamics during cell migration and epithelial morphogenesis. |
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| Keywords: | APC dishevelled focal adhesion migration Wnt5a |
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