한빛사논문
Abstract
Ren Sheng1,*, Hyunjoon Kim2,*, Hyeyoon Lee2,*, Yao Xin1,*, Yong Chen1, Wen Tian1, Yang Cui1, Jong-Cheol Choi3, Junsang Doh3, Jin-Kwan Han2 & Wonhwa Cho1
1 Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, USA. 2Divisions of Molecular and Life Sciences, Pohang 790-784, Korea. 3 Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, Korea. * These authors contributed equally to this work.
Correspondence to: Jin-Kwan Han or Wonhwa Cho
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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