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Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling

Author

Listed:
  • Ren Sheng

    (University of Illinois at Chicago)

  • Hyunjoon Kim

    (Divisions of Molecular and Life Sciences)

  • Hyeyoon Lee

    (Divisions of Molecular and Life Sciences)

  • Yao Xin

    (University of Illinois at Chicago)

  • Yong Chen

    (University of Illinois at Chicago)

  • Wen Tian

    (University of Illinois at Chicago)

  • Yang Cui

    (University of Illinois at Chicago)

  • Jong-Cheol Choi

    (Pohang University of Science and Technology)

  • Junsang Doh

    (Pohang University of Science and Technology)

  • Jin-Kwan Han

    (Divisions of Molecular and Life Sciences)

  • Wonhwa Cho

    (University of Illinois at Chicago)

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.

Suggested Citation

  • Ren Sheng & Hyunjoon Kim & Hyeyoon Lee & Yao Xin & Yong Chen & Wen Tian & Yang Cui & Jong-Cheol Choi & Junsang Doh & Jin-Kwan Han & Wonhwa Cho, 2014. "Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5393
    DOI: 10.1038/ncomms5393
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    Cited by:

    1. Alfredo Erazo-Oliveras & Mónica Muñoz-Vega & Mohamed Mlih & Venkataramana Thiriveedi & Michael L. Salinas & Jaileen M. Rivera-Rodríguez & Eunjoo Kim & Rachel C. Wright & Xiaoli Wang & Kerstin K. Landr, 2023. "Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    2. Fabiola Diniz & Nguyen Yen Nhi Ngo & Mariel Colon-Leyva & Francesca Edgington-Giordano & Sylvia Hilliard & Kevin Zwezdaryk & Jiao Liu & Samir S. El-Dahr & Giovane G. Tortelote, 2023. "Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Julien Bous & Julia Kinsolving & Lukas Grätz & Magdalena M. Scharf & Jan Hendrik Voss & Berkay Selcuk & Ogün Adebali & Gunnar Schulte, 2024. "Structural basis of frizzled 7 activation and allosteric regulation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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