Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Characterization of a multicomponent receptor for GDNF

Nature volume 382, pages 80–83 (1996)Cite this article

Abstract

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF)1 is a potent survival factor for central and peripheral neurons2–6, and is essential for the development of kidneys and the enteric nervous system7–9. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive cells and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret10–12, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lin, L. H., Doherty, D. H., Lile, J. D., Bektesh, S. & Collins, F. Science 260, 1130–1132 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Buj-Bell, A., Buchman, V. L., Horton, A., Rosenthal, A. & Davies, A. M. Neuron 15, 821–828 (1995).

    Article  Google Scholar 

  3. Beck, K. D. et al. Nature 373, 339–341 (1995).

    Article  ADS  CAS  Google Scholar 

  4. Tomac, A. et al. Nature 373, 335–359 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Henderson, C. E. et al. Science 266, 1062–1064 (1994).

    Article  ADS  CAS  Google Scholar 

  6. Arenas, E., Trupp, M., Akerud, P. & Ibáñez, C. F. Neuron 15, 1465–1473 (1995).

    Article  CAS  Google Scholar 

  7. Pichel, J. S. et al. Nature 382, 73–76 (1996).

    Article  ADS  CAS  Google Scholar 

  8. Sanchez, M. P. et al. Nature 382, 70–73 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Moore, M. W. et al. Nature 382, 76–79 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Takahashi, M., Ritz, J. & Cooper, G. M. Cell 42, 581–588 (1985).

    Article  CAS  Google Scholar 

  11. Takahashi, M. & Cooper, G. M. Molec. cell. Biol. 7, 1378–1385 (1987).

    Article  CAS  Google Scholar 

  12. Takahashi, M. Crit. Rev. Oncogen. 6, 35–46 (1995).

    Article  CAS  Google Scholar 

  13. Gearing, D. P., King, J. A., Gough, N. M. & Nicola, N. A. EMBO J. 8, 3667–3676 (1989).

    Article  CAS  Google Scholar 

  14. Bazan, J. F. Proc. natn. Acad. Sci. U.S.A. 87, 6934–6938 (1990).

    Article  ADS  CAS  Google Scholar 

  15. Micanovic, R., Gerber, L. D., Berger, J., Kodukula, K. & Udenfriend, S. Proc. natn. Acad. Sci. U.S.A. 87, 157–161 (1990).

    Article  ADS  CAS  Google Scholar 

  16. Koke, J. A., Yang, M., Henner, D. J., Volwerk, J. J. & Griffith, O. H. Prot. Express. Purif. 2, 51–58 (1991).

    Article  CAS  Google Scholar 

  17. Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Costantini, F. & Pachnis, V. Nature 367, 380–383 (1994).

    Article  ADS  CAS  Google Scholar 

  18. Durbec, P. L., Larsson-Blomberg, L. B., Schuchardt, A., Costantini, F. & Pachnis, V. Development 122, 349–358 (1996).

    CAS  Google Scholar 

  19. Pachnis, V., Mankoo, B. & Costantini, F. Development 119, 1005–1007 (1993).

    CAS  Google Scholar 

  20. Avantaggiato, V. et al. Cell Growth Diff. 5, 305–311 (1994).

    CAS  PubMed  Google Scholar 

  21. Tsuzuki, T. et al. Oncogene 10, 191–198 (1995).

    CAS  Google Scholar 

  22. Davis, S. et al. Science 259, 1736–1739 (1993).

    Article  ADS  CAS  Google Scholar 

  23. Lee, J.-D. et al. Proc. natn. Acad. Sci. U.S.A. 90, 9930–9934 (1993).

    Article  ADS  CAS  Google Scholar 

  24. Pugin, J. et al. Proc. natn. Acad. Sci. U.S.A. 90, 2744–2748 (1993).

    Article  ADS  CAS  Google Scholar 

  25. Brown, D. Curr. Opin. Immunol. 5, 349–354 (1993).

    Article  CAS  Google Scholar 

  26. Glass, D. J. et al. Cell 85, 513–523 (1996).

    Article  CAS  Google Scholar 

  27. McDonald, N. Q. & Hendrickson, W. A. Cell 73, 421–424 (1993).

    Article  CAS  Google Scholar 

  28. Poulsen, K. T. et al. Neuron 13, 1245–1252 (1994).

    Article  CAS  Google Scholar 

  29. Loeb, D. M. et al. Cell 66, 961–966 (1991).

    Article  CAS  Google Scholar 

  30. Attisano, L., Wrana, J. L., López-Casillas, F. & Massagué, J. Biochim. biophys. Acta 1222, 21–80 (1994).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    James J. S. Treanor, Laurie Goodman, Donna M. Stone, Kris T. Poulsen, Claus D. Beck, Mark P. Armanini, Franz Hefti, Heidi S. Phillips & Arnon Rosenthal

  2. Department of Molecular Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Christa Gray, Audry Goddard & Mark W. Moore

  3. Department of Protein Biochemistry, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Richard Vandlen

  4. Department of Molecular Cancer Research, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Frederic de Sauvage

  5. INSERM U.382, IBDM, Campus de Luminy–Case 907, 13288, Marseille,Cedex, 09, France

    Richard A. Pollock & Christopher E. Henderson

  6. University of St Andrews, Bute Medical Building, St Andrews, Fife, KY16 9AT, UK

    Anna Buj-Bello & Alun M. Davies

  7. Department of Pathology, Nagoya University, Nagoya, 466, Japan

    Naoya Asai & Masahide Takahashi

Authors
  1. James J. S. Treanor
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Laurie Goodman
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Frederic de Sauvage
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Donna M. Stone
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Kris T. Poulsen
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Claus D. Beck
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Christa Gray
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Mark P. Armanini
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Richard A. Pollock
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Franz Hefti
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Heidi S. Phillips
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Audry Goddard
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Mark W. Moore
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Anna Buj-Bello
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Alun M. Davies
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Naoya Asai
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Masahide Takahashi
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Richard Vandlen
    View author publications

    You can also search for this author inPubMed Google Scholar

  19. Christopher E. Henderson
    View author publications

    You can also search for this author inPubMed Google Scholar

  20. Arnon Rosenthal
    View author publications

    You can also search for this author inPubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Treanor, J., Goodman, L., de Sauvage, F. et al. Characterization of a multicomponent receptor for GDNF. Nature 382, 80–83 (1996). https://doi.org/10.1038/382080a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/382080a0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing