LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation

22Citations
Citations of this article
33Readers
Mendeley users who have this article in their library.

Abstract

Canonical Wnt/β-catenin signaling pathway plays important roles in multiple aspects of cellular responses in development and diseases. It is currently thought that Wnt receptor Frizzled (Frz) exists separately to Wnt coreceptors LRP5 and LRP6 (LRP5/6), and that Wnt-Frz-LRP5/6 triple complex formation bridged by Wnt ligand is needed for canonical pathway activation. We recently showed that Frz and LRP5/6 interact with each other in the absence of Wnt ligand binding and this interaction maintains the Frz-LRP5/6 complex in an inactive state. Here, we further show that Wnt ligand stimulation induces conformational change of the Frz-LRP6 complex and leads to hexamer formation containing the core LDLR domain-mediated LRP6 homodimer that is stabilized by two pairs of Wnt3a and Frz8, that is, Wnt3a-Frz8 LRP6-LRP6-Frz8-Wnt3a. This LDLR-mediated LRP6 dimerization is essential for robust canonical Wnt pathway activation. Our study thus suggests a previously unrecognized mode of receptor interaction in Wnt signal initiation. © 2014 Elsevier Inc.

Cite

CITATION STYLE

APA

Chen, J., Yan, H., Ren, D. ni, Yin, Y., Li, Z., He, Q., … Zhu, W. (2014). LRP6 dimerization through its LDLR domain is required for robust canonical Wnt pathway activation. Cellular Signalling, 26(5), 1068–1074. https://doi.org/10.1016/j.cellsig.2013.12.020

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free