Cholesterol Selectively Activates Canonical Wnt Signalling over Non-canonical Wnt Signalling

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Jul 16

PMID 25024088

Citations 79

Authors

Ren Sheng

Hyunjoon Kim

Hyeyoon Lee

Yao Xin

Yong Chen

Wen Tian

Yang Cui

Jong-Cheol Choi

Junsang Doh

Jin-Kwan Han

Wonhwa Cho

Affiliations

Soon will be listed here.

Abstract

Wnt proteins control diverse biological processes through β-catenin-dependent canonical signalling and β-catenin-independent non-canonical signalling. The mechanisms by which these signalling pathways are differentially triggered and controlled are not fully understood. Dishevelled (Dvl) is a scaffold protein that serves as the branch point of these pathways. Here, we show that cholesterol selectively activates canonical Wnt signalling over non-canonical signalling under physiological conditions by specifically facilitating the membrane recruitment of the PDZ domain of Dvl and its interaction with other proteins. Single-molecule imaging analysis shows that cholesterol is enriched around the Wnt-activated Frizzled and low-density lipoprotein receptor-related protein 5/6 receptors and plays an essential role for Dvl-mediated formation and maintenance of the canonical Wnt signalling complex. Collectively, our results suggest a new regulatory role of cholesterol in Wnt signalling and a potential link between cellular cholesterol levels and the balance between canonical and non-canonical Wnt signalling activities.

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