Model for PIP3-driven Rac regulation. The Rac GEF P-Rex1 (red connector) is the major (though not only) PIP3-activated Rac GEF. Downstream of Rac*, actin polymerization and ArhGAP15 function in parallel pathways (blue connectors) to inhibit Rac*. ArhGAP15 activity may require Rac* or be stimulated independently (black dashed arrows). Our data and previous studies are consistent with ArhGAP15 functioning in a negative feedback loop and/or an incoherent feedforward loop to regulate Rac (Costa et al., 2007; Radu et al., 2013). These interactions are masked by additional feedback and redundancy (gray arrows) when input is delivered at the level of the chemoattractant receptor but are revealed when input is delivered at the level of PIP3 production via optogenetics (red lightning bolt).