Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1.

Carlo D Cristobal, Qi Ye, Juyeon Jo, Xiaoyun Ding, Chih-Yen Wang, Diego Cortes, Zheng Chen, Hyun Kyoung Lee

Journal of cell science 2021 Jan 25

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Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify downstream signaling. However, the molecular processes that coordinate these events remain poorly defined. Here, we show that Daam2 regulates canonical Wnt signaling via the PIP2-PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies - in chick spinal cord and human and monkey cell lines - highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering. © 2021. Published by The Company of Biologists Ltd.

Citation

Carlo D Cristobal, Qi Ye, Juyeon Jo, Xiaoyun Ding, Chih-Yen Wang, Diego Cortes, Zheng Chen, Hyun Kyoung Lee. Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1. Journal of cell science. 2021 Jan 25;134(2)