title: Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling.
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.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Ren
authors.initials: R
authors.lastname: Sheng
authors.affiliation: Divisions of Molecular and Life Sciences.
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Divisions of Molecular and Life Sciences.
authors.forename: Hyeyoon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Mechanical Engineering, Pohang University of Science and Technology, Pohang, 790-784, Korea.
authors.forename: Jong-Cheol
authors.initials: JC
authors.lastname: Choi
authors.affiliation: Mechanical Engineering, Pohang University of Science and Technology, Pohang, 790-784, Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Doh
authors.affiliation: Divisions of Molecular and Life Sciences.
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Han
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Cho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism*; D000072261:Dishevelled Proteins; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D002784:Cholesterol