SLIT2 ligand forms a complex with the ROBO1 receptor (Brose et al. 1999). The SLIT family consists of three members that are all expressed in the ventral midline (floor plate) of the neural tube. SLIT1 is predominantly expressed in the nervous system whereas SLIT2 and SLIT3 are also expressed outside the nervous system.
SLIT proteins are the ligands for the ROBO receptors. In humans, there are four ROBO genes: ROBO1, ROBO2, ROBO3 and ROBO4. The extracellular domain of ROBO comprises five Ig domains and three FN domains except for ROBO4 (two Ig + two FN). Ig1 and Ig2 domains of ROBO1 and ROBO2 are highly conserved and are important for SLIT binding. The concave face of SLIT's second LRR domain accommodates the Ig1 and Ig2 domains of ROBO1 and ROBO2. ROBO3 does not bind SLITs (Camurri et al. 2005, Mambetisaeva et al. 2005, Zelina et al. 2014, Jaworski et al. 2015). SLIT binding with ROBO4 is controversial as the interaction is weak and it has been observed using the in-vitro methods (Wang et al. 1999, Brose et al. 1999, Piper et al. 2003, Andrews et al. 2007).
Binding of secreted (cleaved) SLIT2 to ROBO1 and ROBO2 is involved in fasciculation (bundling) of motor axons, which facilitates axon pathfinding and muscle innervation (Jaworski and Tessier-Lavigne 2012).