The phosphoinositide-binding protein p40<i>phox</i> activates the NADPH oxidase during FcγIIA receptor–induced phagocytosis

Suh, Chang-Il; Stull, Natalie D.; Li, Xing Jun; Tian, Wei; Price, Marianne O.; Grinstein, Sergio; Yaffe, Michael B.; Atkinson, Simon J.; Dinauer, Mary C.

doi:10.1083/jcb1744oia8

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…Neutrophils can internalise opsonised particles which are recognised by Fcg receptors (Lin et al, 1994). Although phagocytosis of opsonised zymosan or latex beads by DMF-and DMSO-differentiated PLB-985 cells has been analysed by confocal or phase contrast microscopy, quantification of phagocytosis has not been reported in these cells (Perkins et al, 1991;Suh et al, 2006;van Bruggen et al, 2004). PLB-985 cells differentiated with dbcAMP, DMF, and DMSO were able to phagocytose serumopsonised zymosan A particles, but their phagocytic capacity was weaker than that of neutrophils.…”

Section: Article In Pressmentioning

confidence: 90%

Characterisation of degranulation and phagocytic capacity of a human neutrophilic cellular model, PLB-985 cells☆

et al. 2010

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Section: Article In Pressmentioning

confidence: 90%

Characterisation of degranulation and phagocytic capacity of a human neutrophilic cellular model, PLB-985 cells☆

et al. 2010

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“…Membrane stabilisation and indeed activation of the oxidase also involve phospholipid binding to the Phox homology (PX) domains of p47 phox and p40 phox (termed ‘p40PX’ and ‘p47PX’ hereafter) ( Bravo et al, 2001; Ellson et al, 2001b; Kanai et al, 2001; Karathanassis et al, 2002; Kuribayashi et al, 2002; Suh et al, 2006 ). These two PX domains display different lipid specificities so that p40PX recognises phosphatidylinositol-3-phosphate (PI(3)P) and p47PX recognises phosphatidylinositol-3,4-bisphosphate ( Kanai et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Subcellular localisation of the p40phox component of NADPH oxidase involves direct interactions between the Phox homology domain and F-actin

Shao

Segal

Dekker

2010

The International Journal of Biochemistry & Cell Biology

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Cytosolic components of the NADPH oxidase interact with the actin cytoskeleton. These interactions are thought to be important for the activation of this enzyme system but they are poorly characterised at the molecular level. Here we have explored the interaction between the actin cytoskeleton and p40phox, one of the cytosolic components of NADPH oxidase. Full length p40phox expressed in COS cells co-localised with F-actin in a peripheral lamellar compartment. The co-localisation was lost after deletion of the Phox homology (PX) domain and the PX domain in isolation (p40PX) showed the same F-actin co-localisation as the full length protein. PX domains are known lipid-binding modules however, a mutant p40PX which did not bind lipids still co-localised with F-actin suggesting that lipid-independent interactions underlie the localisation. Affinity chromatography identified actin as a binding partner for p40PX in neutrophil extracts. Pure actin interacted with both p40phox and with p40PX suggesting it is a direct interaction. Disruption of the actin cytoskeleton with cytochalasin D resulted in actin rearrangement and concomitantly the localisation of full length p40phox proteins and that of p40PX changed. Thus p40PX is a dual F-actin/lipid-binding module and F-actin interactions with the PX domain dictate at least in part the intracellular localisation of the cytosolic p40phox subunit of the NADPH oxidase.

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“…However, the intermediate steps that link depolarization and NOX2 activation are not clear. Previous studies (1,8,22,36,41) have implicated phosphoinositide 3-kinase (PI3K) in the activation of NOX2 in various cell systems. We (44) have previously shown in the isolated mouse lung that wortmannin, a PI3K inhibitor, prevents the translocation of NOX2 subunits and reduces ROS production with ischemia.…”

mentioning

confidence: 99%

Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS

Chatterjee

Browning

Hong

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

126

122

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Loss of fluid shear stress (ischemia) to the lung endothelium causes endothelial plasma membrane depolarization via ATP-sensitive K(+) (K(ATP)) channel closure, initiating a signaling cascade that leads to NADPH oxidase (NOX2) activation and ROS production. Since wortmannin treatment significantly reduces ROS production with ischemia, we investigated the role of phosphoinositide 3-kinase (PI3K) in shear-associated signaling. Pulmonary microvascular endothelial cells in perfused lungs subjected to abrupt stop of flow showed membrane depolarization and ROS generation. Stop of flow in flow-adapted mouse pulmonary microvascular endothelial cells in vitro resulted in the activation of PI3K and Akt as well as ROS generation. ROS generation in the lungs in situ was almost abolished by the PI3K inhibitor wortmannin and the PKC inhibitor H7. The combination of the two (wortmannin and H7) did not have a greater effect. Activation of NOX2 was greatly diminished by wortmannin, knockout of Akt1, or dominant negative PI3K, whereas membrane depolarization was unaffected. Ischemia-induced Akt activation (phosphorylation) was not observed with K(ATP) channel-null cells, which showed minimal changes in membrane potential with ischemia. Activation of Akt was similar to wild-type cells in NOX2-null cells, which do not generate ROS with ischemia. Cromakalim, a K(ATP) channel agonist, prevented both membrane depolarization and Akt phosphorylation with ischemia. Thus, Akt1 phosphorylation follows cell membrane depolarization and precedes the activation of NOX2. These results indicate that PI3K/Akt and PKC serve as mediators between endothelial cell membrane depolarization and NOX2 assembly.

show abstract

The phosphoinositide-binding protein p40phox activates the NADPH oxidase during FcγIIA receptor–induced phagocytosis

Cited by 6 publications

References 40 publications

Characterisation of degranulation and phagocytic capacity of a human neutrophilic cellular model, PLB-985 cells☆

Characterisation of degranulation and phagocytic capacity of a human neutrophilic cellular model, PLB-985 cells☆

Subcellular localisation of the p40phox component of NADPH oxidase involves direct interactions between the Phox homology domain and F-actin

Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS

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