SLIT2-activated ROBO1 receptor can form a complex with a G-protein coupled receptor (GPCR) CXCR4 (Prasad et al. 2007), resulting in downregulation of CXCR4 signaling (Prasad et al. 2004, Prasad et al. 2007). Formation of the complex between ROBO1 and CXCR4, which involves the CC3 motif of ROBO1, does not interfere with CXCR4 binding to its ligand, CXCL12 (Prasad et al. 2007). SLIT-ROBO signaling may also downregulate CXCR4 expression (Marlow et al. 2008). Downregulation of CXCL12-CXCR4 signaling is thought to contribute to SLIT-ROBO-mediated inhibition of cell migration (Prasad et al. 2004, Prasad et al. 2007, Marlow et al. 2008).