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Crème de la Kremen of Wnt signalling inhibition

Nature Cell Biology volume 4, page E172 (2002)Cite this article

Embryonic development depends on spatially regulated signals that function locally to change the fate or shape of cells. Recent advances have shed light on a sophisticated mechanism of Wnt signal inhibition, whereby an activating coreceptor, LDL-receptor-related protein 6 (LRP6), is segregated away by a secreted inhibitor (Dickkopf) and removed by internalization after interaction with the membrane-anchored protein, Kremen.

Kremen was identified in a transfection screen where pools of cDNAs were transfected into human cell lines and Dkk binding to cells was detected by enzymatic reaction. The ternary complex formation between LRP6, Dkk and Krm was shown elegantly in vivo through bioluminescence resonance energy transfer (BRET)10 experiments. The two membrane-anchored molecules were tagged with Renilla luciferase and yellow fluorescent protein (YFP), respectively, which 'light up' when activated and brought into proximity through the binding of both molecules to Dkk. Such methodology is expected to become an extremely useful tool in studying protein complex formation both outside and inside cells. Two related forms, Kremen-1 and -2 (Krm1 and Krm2), were identified. Although several Dkk molecules also exist, the authors found that Dkk1 and Dkk2, but not Dkk3, bind with high affinity to both Krm1 and Krm2. Because Dkk1 blocks Wnt signalling, but Dkk2 and Dkk3 do not, this suggests a further level of control and raises new questions about their individual specificity. In some instances, Dkk2 may even potentiate Wnt signalling11. Therefore, in the future it will be important to define how the specificity is achieved in vivo.

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Figure 1: A model of canonical Wnt signalling inhibition through Kremen (Krm).

References

  1. Huelsken, J. & Birchmeier, W. Curr. Opin. Genet. Dev. 11, 547–553 (2001).

    Article  CAS  Google Scholar 

  2. Niehrs, C. Nature 413, 787–788 (2001).

    Article  CAS  Google Scholar 

  3. Wehrli, M. et al. Nature 407, 527–530 (2000).

    Article  CAS  Google Scholar 

  4. Mao, B. et al. Nature 417, 664–667 (2002).

    Article  CAS  Google Scholar 

  5. Semenov, M. V. et al. Curr. Biol. 11, 951–961 (2001).

    Article  CAS  Google Scholar 

  6. Glinka, A. et al. Nature 391, 357–362 (1998).

    Article  CAS  Google Scholar 

  7. Mukhopadhyay, M. et al. Dev. Cell 1, 423–434 (2001).

    Article  CAS  Google Scholar 

  8. Bafico, A., Liu, G., Yaniv, A., Gazit, A. & Aaronson, S. A. Nature Cell Biol. 3, 683–686 (2001).

    Article  CAS  Google Scholar 

  9. Mao, B. et al. Nature 411, 321–325 (2001).

    Article  CAS  Google Scholar 

  10. Xu, Y., Piston, D. W. & Johnson, C. H. Proc. Natl Acad. Sci. USA 96, 151–156 (1999).

    Article  CAS  Google Scholar 

  11. Wu, W., Glinka, A., Delius, H. & Niehrs, C. Curr. Biol. 10, 1611–1614 (2000).

    Article  CAS  Google Scholar 

  12. Axelrod, J. D., Miller, J. R., Shulman, J. M., Moon, R. T. & Perrimon, N. Genes Dev. 12, 2610–2622 (1998).

    Article  CAS  Google Scholar 

  13. Wallingford, J. B. et al. Nature 405, 81–85 (2000).

    Article  CAS  Google Scholar 

  14. Hamada, F. et al. Science 283, 1739–1742 (1999).

    Article  CAS  Google Scholar 

  15. Mao, J. et al. Mol. Cell 7, 801–809 (2001).

    Article  CAS  Google Scholar 

  16. Herz, J. Trends Neurosci. 24, 193–195 (2001).

    Article  CAS  Google Scholar 

  17. Dubois, L., Lecourtois, M., Alexandre, C., Hirst, E. & Vincent, J. P. Cell 105, 613–624 (2001).

    Article  CAS  Google Scholar 

Download references

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  1. the Institut de Biologie du Développement de Marseille, Laboratoire de Génétique et Physiologie du Développement, CNRS Université de la Méditerranée, Case 907, Campus de Luminy, Marseille, F-13288, France

    Ute Rothbächer & Patrick Lemaire

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  1. Ute Rothbächer
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Rothbächer, U., Lemaire, P. Crème de la Kremen of Wnt signalling inhibition. Nat Cell Biol 4, E172 (2002). https://doi.org/10.1038/ncb0702-e172

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