Cell-surface heparan sulfate is involved in the repulsive guidance activities of Slit2 protein.
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.
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Rammelkamp Center for Education and Research, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, Ohio 44109, USA. hhu@metrohealth.org
D000818:Animals; D001369:Axons / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000502:physiology*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007395:Interneurons / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein