Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2.
Journal:
Nat. Immunol. 2006 JulAuthors:
Mazaki Y, Hashimoto S, Tsujimura T, Morishige M, Hashimoto A, Aritake K, Yamada A, Nam JM, Kiyonari H, Nakao K, Sabe H
Abstract
In neutrophils, superoxide anion production generally accompanies chemotaxis and functions in killing invading pathogens. The GIT2 GTPase-activating protein binds to the guanine nucleotide-exchange factor alphaPIX. Here we show that GIT2 was necessary for directional chemotaxis and for the suppression of superoxide production in G protein-coupled receptor-stimulated neutrophils. GIT2 was also necessary for the orientation of superoxide production toward chemoattractant sources. GIT2 suppressed t
...[more]he activity of ADP ribosylation factor 1 and was a component of the Gbetagamma subunit-mediated direction-sensing machinery 'downstream' of G protein-coupled receptor signaling. This study establishes a function for GIT2 in linking chemotaxis and superoxide production in neutrophils and shows that loss of GIT2 in vivo leads to an immunodeficient state.[less]
Mesh Headings:
ADP-Ribosylation Factor 1, Actins, Animals, Aspergillosis, Cell Cycle Proteins, Chemotactic Factors, Chemotaxis, Complement C5a, Disease Susceptibility, Enzyme Activation, GTP-Binding Protein beta Subunits, GTP-Binding Protein gamma Subunits, Guanine Nucleotide Exchange Factors, Immunologic Deficiency Syndromes, Interleukin-8, Lung, Lung Diseases, Fungal, Mice, Mice, Inbred C57BL, Mice, Knockout, Multiprotein Complexes, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Phosphatidylinositol Phosphates, Phosphoproteins, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Receptors, G-Protein-Coupled, Recombinant Fusion Proteins, Superoxides, p21-Activated Kinases, rac1 GTP-Binding Protein