| First Author | Zelina P | Year | 2014 |
| Journal | Neuron | Volume | 84 |
| Issue | 6 | Pages | 1258-72 |
| PubMed ID | 25433640 | Mgi Jnum | J:218606 |
| Mgi Id | MGI:5618038 | Doi | 10.1016/j.neuron.2014.11.004 |
| Citation | Zelina P, et al. (2014) Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution. Neuron 84(6):1258-72 |
| abstractText | Development of neuronal circuits is controlled by evolutionarily conserved axon guidance molecules, including Slits, the repulsive ligands for roundabout (Robo) receptors, and Netrin-1, which mediates attraction through the DCC receptor. We discovered that the Robo3 receptor fundamentally changed its mechanism of action during mammalian evolution. Unlike other Robo receptors, mammalian Robo3 is not a high-affinity receptor for Slits because of specific substitutions in the first immunoglobulin domain. Instead, Netrin-1 selectively triggers phosphorylation of mammalian Robo3 via Src kinases. Robo3 does not bind Netrin-1 directly but interacts with DCC. Netrin-1 fails to attract pontine neurons lacking Robo3, and attraction can be restored in Robo3(-/-) mice by expression of mammalian, but not nonmammalian, Robo3. We propose that Robo3 evolution was key to sculpting the mammalian brain by converting a receptor for Slit repulsion into one that both silences Slit repulsion and potentiates Netrin attraction. |
