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LDL-receptor-related protein 6 is a receptor for Dickkopf proteins

Author

Listed:
  • Bingyu Mao

    (Deutsches Krebsforschungszentrum)

  • Wei Wu

    (Deutsches Krebsforschungszentrum)

  • Yan Li

    (Deutsches Krebsforschungszentrum)

  • Dana Hoppe

    (Deutsches Krebsforschungszentrum)

  • Peter Stannek

    (Deutsches Krebsforschungszentrum)

  • Andrei Glinka

    (Deutsches Krebsforschungszentrum)

  • Christof Niehrs

    (Deutsches Krebsforschungszentrum)

Abstract

Wnt glycoproteins have been implicated in diverse processes during embryonic patterning in metazoa. They signal through frizzled-type seven-transmembrane-domain receptors to stabilize β-catenin1,2. Wnt signalling is antagonized by the extracellular Wnt inhibitor dickkopf1 (dkk1), which is a member of a multigene family3. dkk1 was initially identified as a head inducer in Xenopus embryos but the mechanism by which it blocks Wnt signalling is unknown. LDL-receptor-related protein 6 (LRP6) is required during Wnt/β-catenin signalling in Drosophila, Xenopus and mouse, possibly acting as a co-receptor for Wnt4,5,6. Here we show that LRP6 (ref. 7) is a specific, high-affinity receptor for Dkk1 and Dkk2. Dkk1 blocks LRP6-mediated Wnt/β-catenin signalling by interacting with domains that are distinct from those required for Wnt/Frizzled interaction. dkk1 and LRP6 interact antagonistically during embryonic head induction in Xenopus where LRP6 promotes the posteriorizing role of Wnt/β-catenin signalling. Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists.

Suggested Citation

  • Bingyu Mao & Wei Wu & Yan Li & Dana Hoppe & Peter Stannek & Andrei Glinka & Christof Niehrs, 2001. "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins," Nature, Nature, vol. 411(6835), pages 321-325, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6835:d:10.1038_35077108
    DOI: 10.1038/35077108
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    Cited by:

    1. Hyeyoon Lee & Celine Marie Camuto & Christof Niehrs, 2024. "R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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