Single-molecule dynamics of Dishevelled at the plasma membrane and Wnt pathway activation
Wenzhe Ma, Maorong Chen, Hong Mo Kang, Zachary Steinhart, Stéphane Angers, Xi He, Marc W. Kirschner
Abstract
Significance Canonical Wnt signaling is one of the most important and widely distributed pathways in metazoan development. Dishevelled is thought to serve as an essential bridge between the membrane receptors and downstream signaling components, which has the tendency to aggregate in vitro and to form large aggregates of dubious significance in vivo, when overexpressed. To obtain a molecular understanding of the role of Dvl in Wnt signaling, while circumventing these aggregation problems, we have expressed a fluorescent-tagged Dishevelled in cells at its physiological concentration and quantified the size distribution of Dishevelled before and after Wnt treatment. We found that limited oligomerization in response to the Wnt ligand is very dynamic and provides a key step in signal transduction.