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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 promotesmembrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonicalWnt 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 coordinatesmembrane translocation and signalosome clustering.

Original languageEnglish
Article numberjcs251140
JournalJournal of Cell Science
Volume134
Issue number2
DOIs
Publication statusPublished - 2021 Jan

All Science Journal Classification (ASJC) codes

  • Cell Biology

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