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Characterization of a multicomponent receptor for GDNF

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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.

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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
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  2. Laurie Goodman
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  3. Frederic de Sauvage
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  4. Donna M. Stone
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  5. Kris T. Poulsen
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  6. Claus D. Beck
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  7. Christa Gray
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  8. Mark P. Armanini
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  9. Richard A. Pollock
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  10. Franz Hefti
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  11. Heidi S. Phillips
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  12. Audry Goddard
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  13. Mark W. Moore
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  14. Anna Buj-Bello
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  15. Alun M. Davies
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  16. Naoya Asai
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  17. Masahide Takahashi
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  18. Richard Vandlen
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  19. Christopher E. Henderson
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  20. Arnon Rosenthal
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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

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

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