Localizing NADPH oxidase-derived ROS.
Reactive oxygen species (ROS) function as signaling molecules to mediate various biological responses, including cell migration, growth, and gene expression. ROS are diffusible and short-lived molecules. Thus, localizing the ROS signal at the specific subcellular compartment is essential for activating redox signaling events after receptor activation. NADPH (nicotinamide adenine dinucleotide phosphate) oxidase is one of the major sources of ROS in vasculature; it consists of a catalytic subunit (Nox1, Nox2, Nox3, Nox4, or Nox5), p22phox, p47phox, p67phox, and the small guanosine triphosphatase Rac1. Targeting of NADPH oxidase to focal complexes in lamellipodia and membrane ruffles through the interaction of p47phox with the scaffold proteins TRAF4 and WAVE1 provides a mechanism for achieving localized ROS production, which is required for directed cell migration. ROS are believed to inactivate protein tyrosine phosphatases, which concentrate in specific subcellular compartments, thereby establishing a positive feedback system that activates redox signaling pathways to promote cell movement. Additionally, ROS production may be localized through interactions of NADPH oxidase with signaling platforms associated with lipid rafts and caveolae, as well as with endosomes. There is also evidence that NADPH oxidase is found in the nucleus, indicating its involvement in redox-responsive gene expression. This review focuses on targeting of NADPH oxidase to discrete subcellular compartments as a mechanism of localizing ROS and activation of downstream redox signaling events that mediate various cell functions.
Ushio-Fukai
Masuko
M
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA. mfukai@uic.edu
D000818:Animals; D021941:Caveolae / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D022081:Cell Surface Extensions / Q000201:enzymology; D011992:Endosomes / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism* / Q000502:physiology; D015388:Organelles / Q000201:enzymology*; D010084:Oxidation-Reduction; D010940:Plant Proteins / Q000502:physiology; D018517:Plant Roots / Q000378:metabolism; D021122:Protein Subunits; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000201:enzymology; D053449:TNF Receptor-Associated Factor 4; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000502:physiology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000502:physiology
C101203:IQ motif containing GTPase activating protein 1; D010940:Plant Proteins; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D020703:ras GTPase-Activating Proteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D017027:Protein Tyrosine Phosphatases; D020830:rac1 GTP-Binding Protein