The inositol polyphosphate 5‐phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE
The inositol polyphosphate 5‐phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE
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DOI：
10.1111/j.1462-5822.2008.01266.x
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发表时间：
2009-03
影响因子：
3.4
通讯作者：
S. Weber;C. Ragaz;H. Hilbi
中科院分区：
文献类型：
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作者：
S. Weber;C. Ragaz;H. Hilbi
嗜肺军团菌是军团病的病原体，在阿米巴和巨噬细胞的特定空泡内复制。为了形成这些“含军团菌的空泡”（LCV），细菌采用Icm/Dot IV型分泌系统和效应蛋白，其中一些通过宿主糖脂磷脂酰肌醇4-磷酸[PtdIns（4）P]锚在LCV膜上。在这里，我们分析了肌醇多磷酸5-磷酸酶（IP 5 Ps）在L.嗜肺菌感染。细菌复制和LCV形成在缺乏IP 5 P Dd 5 P4的盘状网柄藻中发生得更有效，该IP 5 P Dd 5 P4是人OCRL 1（劳氏眼脑肾综合征）的同源物，涉及逆行内体到高尔基体的运输。表型由Dd 5 P4补充，但不是催化失活的5-磷酸酶。异位表达的Dd 5 P4或OCRL 1定位于D.在巨噬细胞的LCV上也发现了OCRL 1。Dd 5 P4对LCV具有催化活性，并在携带野生型但不携带ΔicmT突变体L的LCV上积累。嗜肺菌OCRL 1的N末端结构域结合L.嗜肺军团菌LpnE，一种参与LCV形成的Sel 1样重复蛋白，定位于LCV并选择性结合PtdIns（3）P。pneumophila并结合与LpnE相关的LCV。
Legionella pneumophila, the causative agent of Legionnaires' disease, replicates within a specific vacuole in amoebae and macrophages. To form these ‘Legionella‐containing vacuoles’ (LCVs), the bacteria employ the Icm/Dot type IV secretion system and effector proteins, some of which anchor to the LCV membrane via the host glycolipid phosphatidylinositol 4‐phosphate [PtdIns(4)P]. Here we analysed the role of inositol polyphosphate 5‐phosphatases (IP5Ps) during L. pneumophila infections. Bacterial replication and LCV formation occurred more efficiently in Dictyostelium discoideum amoebae lacking the IP5P Dd5P4, a homologue of human OCRL1 (Oculocerebrorenal syndrome of Lowe), implicated in retrograde endosome to Golgi trafficking. The phenotype was complemented by Dd5P4 but not the catalytically inactive 5‐phosphatase. Ectopically expressed Dd5P4 or OCRL1 localized to LCVs in D. discoideum via an N‐terminal domain previously not implicated in membrane targeting, and OCRL1 was also identified on LCVs in macrophages. Dd5P4 was catalytically active on LCVs and accumulated on LCVs harbouring wild‐type but not ΔicmT mutant L. pneumophila. The N‐terminal domain of OCRL1 bound L. pneumophila LpnE, a Sel1‐like repeat protein involved in LCV formation, which localizes to LCVs and selectively binds PtdIns(3)P. Our results indicate that OCRL1 restricts intracellular growth of L. pneumophila and binds to LCVs in association with LpnE.