| First Author | Briançon-Marjollet A | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 7 | Pages | 2314-23 |
| PubMed ID | 18212043 | Mgi Jnum | J:134213 |
| Mgi Id | MGI:3785137 | Doi | 10.1128/MCB.00998-07 |
| Citation | Briancon-Marjollet A, et al. (2008) Trio mediates netrin-1-induced Rac1 activation in axon outgrowth and guidance. Mol Cell Biol 28(7):2314-23 |
| abstractText | The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. The guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 activation has not yet been identified. Here, we show that the RhoGEF Trio mediates Rac1 activation in netrin-1 signaling. We found that Trio interacts with the netrin-1 receptor DCC in mouse embryonic brains and that netrin-1-induced Rac1 activation in brain is impaired in the absence of Trio. Trio(-/-) cortical neurons fail to extend neurites in response to netrin-1, while they are able to respond to glutamate. Accordingly, netrin-1-induced commissural axon outgrowth is reduced in Trio(-/-) spinal cord explants, and the guidance of commissural axons toward the floor plate is affected by the absence of Trio. The anterior commissure is absent in Trio-null embryos, and netrin-1/DCC-dependent axonal projections that form the internal capsule and the corpus callosum are defective in the mutants. Taken together, these findings establish Trio as a GEF that mediates netrin-1 signaling in axon outgrowth and guidance through its ability to activate Rac1. |
