| First Author | Llambi F | Year | 2001 |
| Journal | EMBO J | Volume | 20 |
| Issue | 11 | Pages | 2715-22 |
| PubMed ID | 11387206 | Mgi Jnum | J:69877 |
| Mgi Id | MGI:2135698 | Doi | 10.1093/emboj/20.11.2715 |
| Citation | Llambi F, et al. (2001) Netrin-1 acts as a survival factor via its receptors UNC5H and DCC. EMBO J 20(11):2715-22 |
| abstractText | The membrane receptors DCC and UNC5H have been shown to be crucial for axon guidance and neuronal migration by acting as receptors for netrin-1. DCC has also been proposed as a dependence receptor inducing apoptosis in cells that are beyond netrin-1 availability. Here we show that the netrin-1 receptors UNC5H (UNC5H1, UNC5H2, UNC5H3) also act as dependence receptors. UNC5H receptors induce apoptosis, but this effect is blocked in the presence of netrin-1. Moreover, we demonstrate that UNC5H receptors are cleaved in vitro by caspase in their intracellular domains. This cleavage may lead to the exposure of a fragment encompassing a death domain required for cell death induction in vivo. Finally, we present evidence that during development of the nervous system, the presence of netrin-1 is crucial to maintain survival of UNC5H- and DCC-expressing neurons, especially in the ventricular zone of the brainstem. Altogether, these results argue for a role of netrin-1 during the development of the nervous system, not only as a guidance cue but as a survival factor via its receptors DCC and UNC5H. |
