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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 ShengHyunjoon KimHyeyoon LeeYao XinYong ChenWen TianYang CuiJong-Cheol ChoiDoh, JHan, JKWonhwa 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
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한진관HAN, JIN KWAN
Dept of Life Sciences
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