Access

Article

Nature Immunology 7, 724–731 (1 July 2006) | doi:10.1038/ni1349

Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2

Yuichi Mazaki , Shigeru Hashimoto , Tohru Tsujimura , Masaki Morishige , Ari Hashimoto , Kosuke Aritake , Atsuko Yamada , Jin-Min Nam , Hiroshi Kiyonari , Kazuki Nakao & Hisataka Sabe

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 αPIX. 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 the activity of ADP ribosylation factor 1 and was a component of the Gβγ 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.