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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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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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creator	Brose, Katja Bland, Kimberly S Wang, Kuan Hong Arnott, David Henzel, William Goodman, Corey S Tessier-Lavigne, Marc Kidd, Thomas
description	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.
doi_str_mv	10.1016/S0092-8674(00)80590-5
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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. 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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
title	Slit Proteins Bind Robo Receptors and Have an Evolutionarily Conserved Role in Repulsive Axon Guidance
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