Slit Proteins Bind Robo Receptors and Have an Evolutionarily Conserved Role in Repulsive Axon Guidance

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...

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Bibliographic Details
Published in:Cell 1999-03, Vol.96 (6), p.795-806
Main Authors: Brose, Katja, Bland, Kimberly S, Wang, Kuan Hong, Arnott, David, Henzel, William, Goodman, Corey S, Tessier-Lavigne, Marc, Kidd, Thomas
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Axons - physiology
Base Sequence
Cell Line, Transformed
Conserved Sequence
COS Cells
DNA, Complementary
Drosophila
Drosophila Proteins
Evolution, Molecular
Humans
Insect Proteins - genetics
Insect Proteins - metabolism
Mice
Molecular Sequence Data
Motor Neurons - physiology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Protein Processing, Post-Translational
Rats
Receptors, Immunologic - genetics
Receptors, Immunologic - metabolism
Robo receptors
Roundabout Proteins
Sequence Homology, Amino Acid
Slit protein
Slit2 protein
Spinal Cord
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80590-5