A model of how SH3BP1–Rac1 mediates Sema3E-PlexinD1 regulation of cytoskeleton stability. (A) In the absence of Sema3E, SH3BP1 is associated with the PlexinD1 complex, and the active form of Rac1 (Rac1GTP) positively regulates actin polymerization. (B) Upon Sema3E treatment, SH3BP1 dissociates from PlexinD1, becomes activated, and through its RhoGAP domain converts GTP-Rac1 to GDP-Rac1. The decreased Rac1 activity leads to actin depolymerization and cell collapse.