| Literature DB >> 25433640 |
Pavol Zelina1, Heike Blockus1, Yvrick Zagar1, Amélie Péres2, François Friocourt1, Zhuhao Wu3, Nicolas Rama1, Coralie Fouquet4, Erhard Hohenester5, Marc Tessier-Lavigne3, Jörn Schweitzer6, Hugues Roest Crollius2, Alain Chédotal7.
Abstract
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.Entities:
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Year: 2014 PMID： 25433640 DOI： 10.1016/j.neuron.2014.11.004
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173