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Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor

Author

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  • Véronique Corset

    (Laboratoire Apoptose et Différenciation, label ‘La Ligue’ – Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1)

  • Kim Tuyen Nguyen-Ba-Charvet

    (INSERM U106, Hôpital de la salpetriere)

  • Christelle Forcet

    (Laboratoire Apoptose et Différenciation, label ‘La Ligue’ – Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1)

  • Emmanuel Moyse

    (Laboratoire Apoptose et Différenciation, label ‘La Ligue’ – Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1)

  • Alain Chédotal

    (INSERM U106, Hôpital de la salpetriere)

  • Patrick Mehlen

    (Laboratoire Apoptose et Différenciation, label ‘La Ligue’ – Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1)

Abstract

The netrins, a family of laminin-related secreted proteins, are critical in controlling axon elongation and pathfinding1,2,3,4. The DCC (for deleted in colorectal cancer) protein was proposed as a receptor for netrin-1 in the light of many observations including the inhibition of netrin-1-mediated axon outgrowth and attraction in the presence of an anti-DCC antiserum5,6,7, the similitude of nervous system defects in DCC and netrin-1 knockout mice4,8 and the results of receptor swapping experiments9. Previous studies have failed to show a direct interaction of DCC with netrin-1 (ref. 10), suggesting the possibility of an additional receptor or co-receptor. Here we show that DCC interacts with the membrane-associated adenosine A2b receptor, a G-protein-coupled receptor that induces cAMP accumulation on binding adenosine11. We show that A2b is actually a netrin-1 receptor and induces cAMP accumulation on binding netrin-1. Finally, we show that netrin-1-dependent outgrowth of dorsal spinal cord axons directly involves A2b. Together our results indicate that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b.

Suggested Citation

  • Véronique Corset & Kim Tuyen Nguyen-Ba-Charvet & Christelle Forcet & Emmanuel Moyse & Alain Chédotal & Patrick Mehlen, 2000. "Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor," Nature, Nature, vol. 407(6805), pages 747-750, October.
  • Handle: RePEc:nat:nature:v:407:y:2000:i:6805:d:10.1038_35037600
    DOI: 10.1038/35037600
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