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 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.
Brose
K
K
Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco 94143-0452, USA.
Bland
K S
KS
Wang
K H
KH
Arnott
D
D
Henzel
W
W
Goodman
C S
CS
Tessier-Lavigne
M
M
Kidd
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D001483:Base Sequence; D019556:COS Cells; D002461:Cell Line, Transformed; D017124:Conserved Sequence; D018076:DNA, Complementary; D004330:Drosophila; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord; D000097905:Roundabout Proteins
D018076:DNA, Complementary; D029721:Drosophila Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C516057:Robo2 protein, rat; C066819:sli protein, Drosophila