A schematic explanation of the phenotypic observations based on the cooperation between Cdc42 targeting and activation. The concentration of active Cdc42^GTP (filled green circles) on the cortex is a fraction of total Cdc42 (filled and open green circles) determined by the GEF activity of Cdc24 boosted by Bem1. Cdc42 localization is controlled by both actin-dependent vesicle (blue circles) trafficking and Rdi1-dependent (purple crescents) pathways. Local concentration of active Cdc42^GTP must reach a threshold level (dotted lines) before imposing sufficient feedback for symmetry breaking. (A) Wild-type cells—both Cdc42 activity and localization are maximized. The level of Cdc42^GTP is well above the threshold. (B) bem1Δ cells—GEF activity is reduced but with the localization of total Cdc42 remaining high, the threshold level of Cdc42^GTP is still attained. (C) LatA-treated wild-type cells–elimination of the actin-based target pathway reduces localization of Cdc42, but with high activation, the Cdc42^GTP threshold can still be reached. (D) LatA-treated bem1Δ cells—decreasing both the activation level and the localization of total Cdc42 prevents attainment of the threshold level of Cdc42^GTP for symmetry breaking.