Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: Retargeting to plasma membrane induced by phagocytosis
Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: Retargeting to plasma membrane induced by phagocytosis
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DOI：
10.4049/jimmunol.173.4.2594
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Howard, JC
中科院分区：
文献类型：
--
作者：
Martens, S;Sabel, K;Howard, JC
最近鉴定的p47 GTP酶是已知的针对小鼠细胞内病原体的最有效的细胞自主抗性系统之一。该家族的一个成员LRG-47已被证明对单核细胞增生李斯特菌、刚地弓形虫、结核分枝杆菌和鸟分枝杆菌的体内免疫控制至关重要，可能是通过促进吞噬体的酸化。然而，LRG-47的细胞内定位及其与吞噬体或任何其他膜系统的关联性质尚不清楚。在这项研究中，我们表明，LRG-47是一个高尔基体相关的蛋白质在干扰素刺激的细胞，这是迅速招募到活跃的质膜吞噬作用，并保持与吞噬体，因为它们成熟。我们发现，高尔基定位LRG-47是依赖于C端附近的两亲性螺旋的完整性，而质膜定位依赖于一个身份不明的信号与G结构域。与LRG-47不同，但与已发表的p47抗性GTP酶（GTP酶，GTP）一样，另一种p47 GTP酶（IIGP 1）与内质网相关。然而，与GTP不同，IIGP 1通过N-末端肉豆蔻酰化修饰与内质网相关。因此，p47 GTP酶是与不同膜系统动态相关的多种细胞内防御因子。
The recently identified p47 GTPases are one of the most effective cell-autonomous resistance systems known against intracellular pathogens in the mouse. One member of the family, LRG-47, has been shown to be essential for immune control in vivo of Listeria monocytogenes, Toxoplasma gondii, Mycobacterium tuberculosis, and Mycobacterium avium, possibly by promoting acidification of the phagosome. However, the intracellular localization of LRG-47, and the nature of its association with the phagosomal or any other membrane system is unknown. In this study, we show that LRG-47 is a Golgi-associated protein in the IFN-stimulated cell, which is rapidly recruited to active plasma membrane upon phagocytosis and remains associated with phagosomes as they mature. We show that the Golgi localization of LRG-47 is dependent on the integrity of an amphipathic helix near the C terminus, whereas the plasma membrane localization depends on an unidentified signal associated with the G domain. Unlike LRG-47, but like the published p47 resistance GTPase, IGTP, a further p47 GTPase, IIGP1, is associated with the endoplasmic reticulum. However, unlike IGTP, IIGP1 is associated with the endoplasmic reticulum by an N-terminal myristoylation modification. Thus, the p47 GTPases are a diverse battery of intracellular defense factors dynamically associated with different membrane systems.