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 neu ronal migration and axon growth via interaction with their cellular roundab out receptors (Robos). Here it was shown that Slit2-Robo-1 interactions wer e enhanced by cell-surface heparan sulfate. Removal of heparan sulfate decr eased the affinity of Slit for Robe by about threefold. In addition, remova l of cell-surface heparan sulfate by heparinase III abolished the chemorepu lsive response to Slit2 normally shown by both the migrating neurons and gr owing axons. These results indicate essential roles for cell-surface hepara n sulfate in the repulsive activities of Slit2.