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

Véronique Corset, Kim Tuyen Nguyen-Ba-Charvet, Christelle Forcet, Emmanuel Moyse, Alain Chédotal and Patrick Mehlen ()
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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

Nature, 2000, vol. 407, issue 6805, 747-750

Abstract: 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.

Date: 2000
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DOI: 10.1038/35037600

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