p47(phox) PX domain of NADPH oxidase targets cell membrane via moesin-mediated association with the actin cytoskeleton.
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.
Zhan
Yong
Y
Department of Biological Science, LSB 206, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
He
Dandan
D
Newburger
Peter E
PE
Zhou
G Wayne
GW
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology*; D006224:Cricetinae; D003599:Cytoskeleton / Q000201:enzymology*; D006801:Humans; D020014:K562 Cells; D008840:Microfilament Proteins / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport
D000199:Actins; D008840:Microfilament Proteins; D010743:Phospholipids; D010750:Phosphoproteins; C071058:moesin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1