PUBLICATION
Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution
- Authors
- Zelina, P., Blockus, H., Zagar, Y., Péres, A., Friocourt, F., Wu, Z., Rama, N., Fouquet, C., Hohenester, E., Tessier-Lavigne, M., Schweitzer, J., Roest Crollius, H., Chédotal, A.
- ID
- ZDB-PUB-170214-262
- Date
- 2014
- Source
- Neuron 84: 1258-72 (Journal)
- Registered Authors
- Schweitzer, Jörn, Tessier-Lavigne, Marc
- Keywords
- none
- MeSH Terms
-
- Animals
- Axons/metabolism*
- Biological Evolution*
- Cell Movement
- Glycoproteins/metabolism
- Humans
- Membrane Proteins/metabolism*
- Mice
- Nerve Growth Factors/metabolism
- Nerve Tissue Proteins/metabolism*
- Receptors, Cell Surface/metabolism*
- Signal Transduction*
- Tumor Suppressor Proteins/metabolism
- Zebrafish
- src-Family Kinases/metabolism
- PubMed
- 25433640 Full text @ Neuron
Citation
Zelina, P., Blockus, H., Zagar, Y., Péres, A., Friocourt, F., Wu, Z., Rama, N., Fouquet, C., Hohenester, E., Tessier-Lavigne, M., Schweitzer, J., Roest Crollius, H., Chédotal, A. (2014) Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution. Neuron. 84:1258-72.
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.
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