Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling
SCIE
SCOPUS
- Title
- Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling
- Authors
- Ren Sheng; Hyunjoon Kim; Hyeyoon Lee; Yao Xin; Yong Chen; Wen Tian; Yang Cui; Jong-Cheol Choi; Doh, J; Han, JK; Wonhwa Cho
- Date Issued
- 2014-07
- Publisher
- Nature communications
- Abstract
- Wnt proteins control diverse biological processes through beta-catenin-dependent canonical signalling and beta-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.
- Keywords
- CONVERGENT EXTENSION MOVEMENTS; DISHEVELLED DEP DOMAIN; PLASMA-MEMBRANE; BETA-CATENIN; PDZ DOMAIN; PROTEIN INTERACTIONS; CELL POLARITY; BINDING; PATHWAY; INHIBITION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14442
- DOI
- 10.1038/NCOMMS5393
- ISSN
- 2041-1723
- Article Type
- Article
- Citation
- Nature communications, vol. 5, no. 1, page. 4393 - 4406, 2014-07
- Files in This Item:
-
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.