Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance

Cell. 1999 Mar 19;96(6):795-806. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / physiology*
  • Base Sequence
  • COS Cells
  • Cell Line, Transformed
  • Conserved Sequence*
  • 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*
  • Sequence Homology, Amino Acid
  • Spinal Cord

Substances

  • DNA, Complementary
  • Drosophila Proteins
  • Insect Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Robo2 protein, rat
  • roundabout protein
  • sli protein, Drosophila

Associated data

  • GENBANK/AF133270
  • GENBANK/AF133730
  • GENBANK/AF182037