SLIT2 and both its natural cleavage products bind glypican-1 (GPC1), a glycosyl phosphatidyl inositol (GPI) anchored heparan sulfate proteoglycan (HSPG), through its C-terminus. Besides glypican-1, other HSPG may also be involved in SLIT2 binding. GPC1:HSPG is important for high affinity binding of SLIT to its receptor and for the repulsive activity of SLIT. SLIT-ROBO signaling strictly requires binding to heparan sulfate. HSPGs may also modulate the extracellular distribution or stability of SLIT proteins (Ronca et al. 2001, Zhang et al. 2004).
Zhang, F, Ronca, F, Linhardt, RJ, Margolis, RU
Ronca, F, Andersen, JS, Paech, V, Margolis, RU
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