Figure 9. A model of WAVE regulatory complex (WRC) function in Robo1 signaling.

In our proposed model, the WRC binds to Robo1 partly via its WRC-interacting receptor sequence (WIRS) motif. Rac1 is activated downstream of Robo1 (Fan et al., 2003; Wong et al., 2001), which likely activates the complex. Slit binding induces increased WIRS-dependent recruitment of the WRC to Robo1, which is vital to Robo1-mediated repulsive signaling. WRC functions downstream of Robo1 by activating Arp2/3 to remodel the actin cytoskeleton. We hypothesize that these WIRS-WRC-mediated actin rearrangements are more likely to facilitate an initial extension of Slit-induced filopodia than endocytosis or recycling of the Robo1 receptor.