p47phox PX domain of NADPH oxidase targets cell membrane via moesin‐mediated association with the actin cytoskeleton

Abstract

Activation of phagocytic NADPH oxidase requires association of its cytosolic subunits with the membrane-bound flavocytochrome. Extensive phosphorylation of the p47^phox subunit of NADPH oxidase marks the initiation of this activation process. The p47^phox subunit then translocates to the plasma membrane, bringing the p67^phox subunit to cytochrome b558 to form the active NADPH oxidase complex. However, the detailed mechanism for targeting the p47^phox subunit to the cell membrane during activation still remains unclear. Here, we show that the p47^phox PX domain is responsible for translocating the p47^phox subunit to the plasma membrane for subsequent activation of NADPH oxidase. We also demonstrate that translocation of the p47^phox PX domain to the plasma membrane is not due to interactions with phospholipids but rather to association with the actin cytoskeleton. This association is mediated by direct interaction between the p47^phox PX domain and moesin.