Figure 10. Schematic of proposed update to RhoGTPase cycle.

We propose that in addition to the canonical GTPase cycle, GDI can extract active GTPase from the plasma membrane. Based on evidence that GTPase:GDI binding prevents GTP hydrolysis and nucleotide exchange (Hart et al., 1992; Ueda et al., 2001), active GTPase extracted by GDI would still be active upon its release back into the plasma membrane.

Figure 10—figure supplement 1. Schematic of RhoGDI’s role in RhoGTPase zone definition around wounds.

Active Rho (green) and active Cdc42 (red) are activated in discrete, concentric zones that close inward as the wound heals. Cdc42 inactivation is variable throughout its zone, thus its zone is shaped by activation (Burkel et al., 2012). Conversely, the Rho zone is shaped by inactivation as it is subject to RhoGAPs 1/8 at the trailing edge of its zone (Davenport, 2016). Thus, we hypothesize that GDI extracts active Cdc42 throughout the Cdc42 zone and inactive Rho from the trialing edge of the Rho zone.