| First Author | Toyofuku T | Year | 2005 |
| Journal | Nat Neurosci | Volume | 8 |
| Issue | 12 | Pages | 1712-9 |
| PubMed ID | 16286926 | Mgi Jnum | J:103842 |
| Mgi Id | MGI:3610789 | Doi | 10.1038/nn1596 |
| Citation | Toyofuku T, et al. (2005) FARP2 triggers signals for Sema3A-mediated axonal repulsion. Nat Neurosci 8(12):1712-9 |
| abstractText | Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. |
