내용요약(Abstract)
The deletion of unwanted or damaged cells is achieved by finely regulated cleaning process, efferocytosis1. It has been established that RhoA and Rac1 GTPases are antagonistically involved in cytoskeleton organization for clearance of apoptotic cells. Overall, Rac1 and its upstream activators facilitate engulfment of apoptotic cells, whereas RhoA and its downstream effector Rho kinase has an inhibitory role. However, the coordinate actions of Rac1 and RhoA at the individual phagocytic cup would sophisticatedly regulate phagocytic process, which are not fully addressed before. Using FRET biosensors to visualize the spatiotemporal dynamics of Rho family GTPases, here we showed that Rac1 and RhoA coordinately regulate critical points of phagocytic process through turning on/off their activities at precise timing and site. RhoA, a negative regulator, known to be down-regulated during phagocytosis, was transiently up-regulated at the phagocytic cup right before the ingestion of apoptotic cells. Rac1 was up-regulated around phagocytic cup during engulfment then immediately down-regulated ensuing actin disassembly prior to phagosome maturation. Demolition of these dynamic activities of RhoA and Rac1 leaded to uncontrolled engulfment and delayed phagosome maturation, respectively. Our results revealed distinct regulatory roles of Rho family GTPases, RhoA as an engulfment holder and Rac1 as a maturation holder during phagocytosis. We believe our findings provide insight how the phagocytes control determine when and where to eat apoptotic cells as well as to digest. Furthermore, understanding of regulatory mechanism of phagocytosis could be applied to therapeutic approaches based on phagocytosis of immune cells.