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Cytosolic phox proteins interact with and regulate the assembly of coronin in neutrophils

Grogan, A; Reeves, E; Keep, N; Wientjes, F; Totty, NF; Burlingame, AL; ... Segal, AW; + view all (1997) Cytosolic phox proteins interact with and regulate the assembly of coronin in neutrophils. J CELL SCI , 110 3071 - 3081.

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Abstract

The NADPH oxidase generates microbicidal superoxide in phagocytes, and when defective it leads to chronic granulomatous disease (CGD), Oxidase specific proteins in the cytosol, p47(phox) and p67(phox), as well as the small GTP binding protein p21rac are important for activation of superoxide production, Because the activity of this oxidase is normally tightly restricted to the phagocytic vacuole, and its temporal and spatial organisation might he regulated by cytoskeletal proteins, we examined the cytosolic phox proteins for interactions with cytoskeletal elements, p67(phox) copurified with a 57 kDa protein, identified as coronin, an actin binding protein that is important for movement and phagocytosis in Dictyostelium. Binding studies revealed that coronin attaches to the C-terminal half of p40(phox) a binding partner of p67(phox). The phox proteins and coronin had a similar distribution in the cell, and both accumulated around the phagocytic vacuole, PMA activation of adherent neutrophils resulted in a major rearrangement of these proteins, and of actin, which were lost from the periphery of the cell and condensed around the nucleus, The rearrangement of F-actin and coronin in adherent cells, were absent, or markedly diminished, in cells from patients lacking p47(phox) or p67(phox) in which an abnormally large proportion of the coronin was present as part of a large complex, The cytosolic phox proteins might play a regulatory role in the reorganisation of the cytoskeleton accompanying superoxide generation.

Type:Article
Title:Cytosolic phox proteins interact with and regulate the assembly of coronin in neutrophils
Keywords:neutrophil, NADPH oxidase, coronin, cytoskeleton, actin binding protein, chronic granulomatous disease, Dictyostelium, p47(phox), p67(phox), CHRONIC GRANULOMATOUS-DISEASE, RESPIRATORY BURST OXIDASE, ACTIN-BINDING-PROTEIN, CELL-FREE SYSTEM, HUMAN POLYMORPHONUCLEAR LEUKOCYTES, NADPH OXIDASE, PHORBOL ESTER, STIMULATED NEUTROPHILS, KINASE-C, ACTIVATION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Internal Medicine

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