Lipid rafts determine efficiency of NADPH oxidase activation in neutrophils.
We have investigated the contribution of lipid rafts to activation of the NADPH oxidase enzyme system in neutrophils. Membrane-bound NADPH oxidase subunits are present in the lipid raft compartment of neutrophils. Cytosolic NADPH oxidase components are mainly absent from but are recruited to rafts upon Fcgamma receptor activation. In parallel, protein kinase C isotypes are recruited to the rafts. Kinetic analysis of NADPH oxidase activation revealed that rafts determine the onset but not the maximal rate of enzyme activity. Thus lipid rafts serve to physically juxtapose the NADPH oxidase effector, protein kinase C and Fcgamma receptor, resulting in efficient coupling.
Shao
Dongmin
D
Department of Medicine, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK.
Segal
Anthony W
AW
Dekker
Lodewijk V
LV
D002478:Cells, Cultured; D003505:Cyclodextrins / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051745:Protein Kinase C-delta; D021381:Protein Transport; D017452:Receptors, IgG / Q000378:metabolism; D013211:Staphylococcus aureus; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D017452:Receptors, IgG; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta