| Receptor-mediated phagocytosis, a fundamental process, through which cells internalize extracellular particles, requires the function of Rho family GTPases. We found that the Rho GTPase, Cdc42, functions in a size-dependent manner during phagocytosis. That is, large particle uptake required Cdc42 signaling but small particle uptake did not. This result was consistent with the fact that host cell binding by large particles, but not by small ones, activated Cdc42. Furthermore, a link between Cdc42 signaling and endocytic dynamics during phagocytosis was uncovered. Markers of the endocytic network were found on nascent phagosomes in a size-dependent manner, suggesting that only large particle uptake requires membrane delivery from intracellular pools. Additionally, we found that bulk membrane flow to the cell surface is defective in the absence of Cdc42 signaling and that large particle uptake defect observed in the absence of Cdc42 signaling could be suppressed by increasing membrane flow to the cell surface from the recycling endosome. Taken together, these results describe a new function for Cdc42 during phagocytosis that differs from its previously-characterized role in actin rearrangement.;A number of bacterial pathogens such as Yersinia species encode and deliver toxins into the host cell cytosol that misregulate Rho GTPases. Here we show that the Rho GTPase, RhoG, is misregulated by three Y. pseudotuberculosis virulence determinants. Invasin-mediated bacterial binding activates RhoG, while YopE, a translocated Rho GAP, inactivates RhoG. Additionally, the prenylcysteine endoprotease, YopT, cleaves RhoG, thereby mislocalizing it. RhoG is important for proper neutrophil function, so its misregulation may be a way for Y. pseudotuberculosis to avoid immune clearance and thus replicate effectively in the host organism. |
