Autocatalytic RhoA activation and delayed negative feedback through RGA-3/4 is sufficient to produce locally excitable RhoA dynamics. (A) Schematic representation of a simple mathematical model for RhoA pulse dynamics, based on our results. (B and C) Fitting the model to measurements of dRhoA/dt versus RhoA during the rising phase of the pulse (colored traces in B; fit shown in C) to estimate the values of parameters governing autoactivation of RhoA. (D and E) Fitting the model to measurements of dRhoA/dt versus RhoA and RGA-3 during the later phase of the pulse (colored traces in D; fit shown in E) to estimate the values of parameters governing inhibition of RhoA by RGA-3. (F and G) Fitting the model to measurements of dRGA-3/dt versus RhoA and RGA-3 during the entire pulse (colored traces in F; fit shown in G) to estimate the values of parameters governing cortical association and disassociation of RGA-3. See Materials and methods for details of fitting procedures. (H) Comparison between measured (dashed lines) and simulated (solid lines) pulse dynamics for the case in which n = 1, $k r 0 =0.001$⁠, $k p 0 =0.0001$⁠, K_GAP = 0.001, and the remaining model parameters estimated by fitting data are m = 3.02, $kpfb=0.094$⁠, K_fb = 0.12, $krass=0.245$⁠, and $k r diss =0.047$ (see Materials and methods for details). (I) Simulated dynamics for the parameter values in H are excitable, and a stable rest state can be destabilized by a transient reduction of RGA-3/4 (vertical black arrow) to trigger a single pulse of RhoA activity. (J) A small change in the basal RGA-3 association rate from $k p 0 =0.0001$ to $k p 0 =0.001$ results in oscillatory dynamics, with pulses occurring at regular intervals.