Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor.
In: Nature, Jg. 407 (2000-10-12), Heft 6805, S. 747-50
Online
academicJournal
Zugriff:
The netrins, a family of laminin-related secreted proteins, are critical in controlling axon elongation and pathfinding. 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 antiserum, the similitude of nervous system defects in DCC and netrin-1 knockout mice and the results of receptor swapping experiments. 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 adenosine. 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.
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Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor.
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Autor/in / Beteiligte Person: | Corset, V ; Nguyen-Ba-Charvet, KT ; Forcet, C ; Moyse, E ; Chédotal, A ; Mehlen, P |
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Zeitschrift: | Nature, Jg. 407 (2000-10-12), Heft 6805, S. 747-50 |
Veröffentlichung: | Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2000 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/35037600 |
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