Cell-surface Heparan Sulfate Is Involved in the Repulsive Guidance Activities of Slit2 Protein

Nat Neurosci. 2001 Jul;4(7):695-701. doi: 10.1038/89482.


Slit proteins are a family of secreted guidance proteins that can repel neuronal migration and axon growth via interaction with their cellular roundabout receptors (Robos). Here it was shown that Slit2-Robo-1 interactions were enhanced by cell-surface heparan sulfate. Removal of heparan sulfate decreased the affinity of Slit for Robo by about threefold. In addition, removal of cell-surface heparan sulfate by heparinase III abolished the chemorepulsive response to Slit2 normally shown by both the migrating neurons and growing axons. These results indicate essential roles for cell-surface heparan sulfate in the repulsive activities of Slit2.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology
  • Cell Line
  • Cell Movement
  • Fluorescent Antibody Technique
  • Heparan Sulfate Proteoglycans / metabolism
  • Heparitin Sulfate / physiology*
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins
  • Interneurons / physiology
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / ultrastructure
  • Rats
  • Receptors, Immunologic / metabolism


  • Heparan Sulfate Proteoglycans
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • roundabout protein
  • Heparitin Sulfate
  • Slit homolog 2 protein