Slit Proteins Bind Robo Receptors and Have an Evolutionarily Conserved Role in Repulsive Axon Guidance
Open Access
- 1 March 1999
- journal article
- research article
- Published by Elsevier BV in Cell
- Vol. 96 (6), 795-806
- https://doi.org/10.1016/s0092-8674(00)80590-5
Abstract
Extending axons in the developing nervous system are guided in part by repulsive cues. Genetic analysis in Drosophila, reported in a companion to this paper, identifies the Slit protein as a candidate ligand for the repulsive guidance receptor Roundabout (Robo). Here we describe the characterization of three mammalian Slit homologs and show that the Drosophila Slit protein and at least one of the mammalian Slit proteins, Slit2, are proteolytically processed and show specific, high-affinity binding to Robo proteins. Furthermore, recombinant Slit2 can repel embryonic spinal motor axons in cell culture. These results support the hypothesis that Slit proteins have an evolutionarily conserved role in axon guidance as repulsive ligands for Robo receptors.Keywords
This publication has 38 references indexed in Scilit:
- Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptorsNature, 1997
- Interference with Axonin-1 and NrCAM Interactions Unmasks a Floor-Plate Activity Inhibitory for Commissural AxonsNeuron, 1997
- Distribution of the ten known laminin chains in the pathways and targets of developing sensory axonsJournal of Comparative Neurology, 1997
- Deleted in Colorectal Cancer (DCC) Encodes a Netrin ReceptorCell, 1996
- commissureless Controls Growth Cone Guidance across the CNS Midline in Drosophila and Encodes a Novel Membrane ProteinNeuron, 1996
- Sonic hedgehog: making the gradientCell Chemical Biology, 1996
- Chemorepulsion of developing motor axons by the floor plateNeuron, 1995
- The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6Cell, 1994
- Modularity of the slit protein: Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactionsJournal of Molecular Biology, 1992
- slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains.Genes & Development, 1990