FIGURE 8:

Model of Arl4A involvement in Robo1-mediated Cdc42 activation. Robo1 is a single-pass transmembrane receptor. GTP-bound Arl4A can interact with Robo1 via its cytoplasmic CC3 domain. (A) An intermediate Robo1 structure may be associated with an unknown Cdc42 GEF (purple triangles), which is much more susceptible to Cdc42 activation by Arl4A stimulation. (B) More activated Arl4A molecules induce the localization of Robo1 at the plasma membrane and subsequently bind its CC3 domain. The Arl4A-Robo1 interaction prevents srGAP1 from binding Robo1 and promotes Cdc42 activation. (C) Slit2 binding to the amino terminus of Robo1 decreases the Arl4A-Robo1 interaction and enhances the srGAP1-Robo1 interaction, ultimately promoting Cdc42 inactivation.