Letter | Published:

arrow encodes an LDL-receptor-related protein essential for Wingless signalling

Nature volume 407, pages 527530 (28 September 2000) | Download Citation

Subjects

  • A Corrigendum to this article was published on 12 April 2001

Abstract

The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Mechanisms of Wnt signalling in development. Annu. Rev. Cell Dev. Biol. 14, 59– 88 (1998).

  2. 2.

    & wingless generates cell type diversity among engrailed expressing cells. Nature 360, 347–350 (1992).

  3. 3.

    et al. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225–230 (1996).

  4. 4.

    , & Wingless signalling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development 126, 577–586 ( 1999).

  5. 5.

    , & The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev. 8, 118– 130 (1994).

  6. 6.

    , & Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless . Cell 63, 549–560 (1990).

  7. 7.

    et al. Cloning of a novel member of the low–density lipoprotein receptor family. Gene 216, 103– 111 (1998).

  8. 8.

    et al. A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E. J. Biochem. (Tokyo) 124, 1072– 1076 (1998).

  9. 9.

    et al. Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity. Biochem. Biophys. Res. Commun. 251, 784–790 ( 1998).

  10. 10.

    , & Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human. Genomics 55, 314–321 (1999).

  11. 11.

    , & LDL-receptor structure. Calcium cages, acid baths and recycling receptors. Nature 388, 629 –630 (1997).

  12. 12.

    , & Direct and long-range action of a wingless morphogen gradient. Cell 87, 833– 844 (1996).

  13. 13.

    & Long–range action of Wingless organizes the dorsal–ventral axis of the Drosophila wing. Development 124, 871– 880 (1997).

  14. 14.

    & Antagonistic interactions between wingless and decapentaplegic responsible for dorsal–ventral pattern in the Drosophila leg. Science 273, 1373–1377 (1996).

  15. 15.

    & Complementary and mutually exclusive activities of decapentaplegic and wingless organize axial patterning during Drosophila leg development. Cell 86, 401–409 (1996).

  16. 16.

    & Decapentaplegic restricts the domain of wingless during Drosophila limb patterning. Nature 382, 162–164 ( 1996).

  17. 17.

    , , & Shaggy and dishevelled exert opposite effects on Wingless and Decapentaplegic expression and on positional identity in imaginal discs. Development 124, 1069–1078 (1997).

  18. 18.

    & Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404 , 725–728 (2000).

  19. 19.

    , , & Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93, 767–777 (1998).

  20. 20.

    & Wingless transduction by the frizzled and frizzled2 proteins of Drosophila. Development 126, 5441–5452 (1999).

  21. 21.

    , , , & An LDL-receptor-related protein, regulates Wnt signalling in mice. Nature 407, 535– 538 (2000).

  22. 22.

    & Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signalling in the equatorial/polar axis. Development 125, 1421–1432 ( 1998).

  23. 23.

    et al. LDL-receptor-related proteins in Wnt signal transduction. Nature 407, 530–535 ( 2000).

  24. 24.

    , , , & Differential recruitment of Dishevelled provides signalling specificity in the planar cell polarity and Wingless signalling pathways. Genes Dev. 12, 2610– 2622 (1998).

  25. 25.

    & Mutant mice with scrambled brains: understanding the signalling pathways that control cell positioning in the CNS. Genes Dev. 13, 2758– 5873 (1999).

  26. 26.

    , & Proteins of the CNR family are multiple receptors for Reelin. Cell 99, 635–647 ( 1999).

  27. 27.

    & Functional cDNA libraries from Drosophila embryos. J. Mol. Biol. 203, 425–437 (1988).

  28. 28.

    , & Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development 119, 1359–1369 (1993).

  29. 29.

    & Epithelial planar polarity in the developing Drosophila eye. Development 121 , 2451–2459 (1995).

  30. 30.

    , & Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster I Zygotic loci on the second chromosome . Roux's Arch. Dev. Biol. 193 , 267–282 (1984).

Download references

Acknowledgements

G. Campbell, G. Struhl, F. Diaz-Benjumea, S. Cohen, R. Goto-Mandeville, E. Bieschke and B. Calvi provided insightful suggestions and help along the way. The free exchange of information with the Skarnes lab is acknowledged. The manuscript was improved by comments from N. Erdeniz, P. Klein, B. Wilder and the DiNardo lab. Material provided by J. Szidonya, the Bloomington Stock Center and Berkeley Drosophila Genome Project was of great importance. Supported by the Swiss National Science Foundation (M.W.), NIH (A.T. and S.D.) and American Cancer Society (S.D.).

Author information

Author notes

    • Marcel Wehrli
    •  & Scott T. Dougan

    These authors contributed equally to this work

Affiliations

  1. *University of Pennsylvania School of Medicine, BRB II Room 1223, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA

    • Marcel Wehrli
    • , Stephanie Schwartz
    •  & Stephen DiNardo
  2. †Columbia University, 710 West 168th Street, New York, New York 10032, USA

    • Marcel Wehrli
    •  & Andrew Tomlinson
  3. §Rockefeller University, 1230 York Avenue, New York. New York, 10021 , USA

    • Scott T. Dougan
    • , Kim Caldwell
    • , Louise O'Keefe
    • , Stephanie Schwartz
    •  & Stephen DiNardo
  4. Weizmann Institute of Science, Rehovot 76100, Israel

    • Dalit Vaizel-Ohayon
    •  & Eyal Schejter

Authors

  1. Search for Marcel Wehrli in:

  2. Search for Scott T. Dougan in:

  3. Search for Kim Caldwell in:

  4. Search for Louise O'Keefe in:

  5. Search for Stephanie Schwartz in:

  6. Search for Dalit Vaizel-Ohayon in:

  7. Search for Eyal Schejter in:

  8. Search for Andrew Tomlinson in:

  9. Search for Stephen DiNardo in:

Corresponding author

Correspondence to Stephen DiNardo.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Information

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/35035110

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.