Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2
Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2
复制标题
DOI：
10.1038/ni1349
复制
发表时间：
2006-07-01
影响因子：
30.5
通讯作者：
Sabe, Hisataka
中科院分区：
文献类型：
--
作者：
Mazaki, Yuichi;Hashimoto, Shigeru;Sabe, Hisataka
在中性粒细胞中，超氧阴离子的产生通常伴随着趋化性并起到杀死入侵病原体的作用。 GIT2 GTP 酶激活蛋白与鸟嘌呤核苷酸交换因子 α PIX 结合。在这里，我们证明 GIT2 对于定向趋化性和抑制 G 蛋白偶联受体刺激的中性粒细胞中超氧化物的产生是必需的。 GIT2 对于将超氧化物的产生导向化学引诱源也是必要的。 GIT2 抑制 ADP 核糖基化因子 1 的活性，并且是 G β γ 亚基介导的方向传感机制 G 蛋白偶联受体信号传导“下游”的一个组成部分。这项研究确立了 GIT2 在连接中性粒细胞趋化性和超氧化物产生方面的功能，并表明体内 GIT2 的缺失会导致免疫缺陷状态。
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 alpha PIX. 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 G beta gamma 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.