Septin2 regulates <scp>ARHGAP</scp>25‐mediated suppression of lamellipodia formation and cell spreading

Rho family small GTPases are key regulators of the actin cytoskeletal organization that controls cell morphology, but the regulatory mechanism of Rho small GTPase activity is not fully understood. Here we identified septin2, a component of the septin cytoskeleton, as an interacting protein of ARHGAP25, a GTPase-activating protein for Rho small GTPase Rac, in mammalian cells. ARHGAP25 colocalized with septin2 at lamellipodia, which are actin filament-rich protrusions. Overexpression of ARHGAP25 suppressed Rac-dependent lamellipodia formation and cell spreading, and ARHGAP25-mediated suppression was restored by depletion of septin2. Forced expression of septin2 enhanced ARHGAP25-mediated suppression of cell spreading, and septin2-enhanced suppression was restored by the depletion of ARHGAP25. These results suggest that septin2 controls cell morphology by regulating the function of ARHGAP25.