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Br J Pharmacol. 2017 Dec;174(24):4564-4574. doi: 10.1111/bph.14048. Epub 2017 Oct 18.

Assembly and architecture of the Wnt/β-catenin signalosome at the membrane.

Author information

1
Center for Cancer and Cell Biology, Laboratory for Structural Biology and Biochemistry, Van Andel Research Institute, Grand Rapids, MI, USA.
2
Center for Cancer and Cell Biology, Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, MI, USA.
3
Van Andel Research Institute/Shanghai Institute of Materia Medica Center, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Abstract

Wnt/β-catenin signalling is initiated by a ternary Wnt-Frizzled (FZD)-LDL receptor-related protein (LRP) 5/6 binding event. The resulting conformational changes in the FZD and LRP5/6 receptors promote the assembly of an intracellular signalosome driven by Dishevelled and Axin co-polymerization. Recent evidence suggests that the FZD receptor and LRP5/6 participate in the assembly of this signalosome by forming regulatory scaffolds for stabilizing Dishevelled and Axin adapters. In this review, we focus on the contributions of Wnts and their receptors in the assembly of the signalosome. We present an emerging model, which unifies Wnt receptor oligomerization with intracellular signalosome formation, and then discuss how FZD receptors might be targeted to either disrupt or enhance their capacity as a dynamic sensor of Wnt binding.

LINKED ARTICLES:

This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.

PMID:
28941231
PMCID:
PMC5727340
DOI:
10.1111/bph.14048
[Indexed for MEDLINE]
Free PMC Article

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