Modulation of ubiquitin dynamics and suppression of DALIS formation by the Legionella pneumophila Dot/Icm system.
Modulation of ubiquitin dynamics and suppression of DALIS formation by the Legionella pneumophila Dot/Icm system.
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DOI：
10.1111/j.1462-5822.2008.01251.x
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发表时间：
2009-02
影响因子：
3.4
通讯作者：
Roy CR
中科院分区：
文献类型：
--
作者：
Ivanov SS;Roy CR
嗜肺军团菌是一种细胞内病原体，它利用Dot/Icm IV型分泌系统易位的效应蛋白来调节宿主细胞过程。在这里，我们研究了含泛素的亚细胞结构在嗜肺乳杆菌侵染吞噬宿主细胞时的动态变化。Dot/Icm系统介导巨噬细胞和树突状细胞中K48和K63多泛素偶联物与含嗜肺乳杆菌液泡相关蛋白的形成，表明在感染过程中涉及泛素的调节事件和降解事件受到细菌效应物的调节。嗜肺乳杆菌衍生分子刺激巨噬细胞和树突状细胞表面的TLR2可产生富含泛素的树突状细胞聚集体样结构（DALIS）。然而，用Dot/Icm系统感染嗜肺乳杆菌的细胞不能产生DALIS。抑制DALIS的形成不影响含嗜肺乳杆菌液泡上泛素化蛋白的积累。对其他种类军团菌的研究表明，约旦军团菌在形成泛素修饰的液泡后无法抑制DALIS的形成。因此，嗜肺L. Dot/Icm系统能够调节宿主过程，促进K48和K63泛素在液泡膜蛋白上结合，并独立抑制DALIS形成所需的细胞事件。
Legionella pneumophila is an intracellular pathogen that uses effector proteins translocated by the Dot/Icm type IV secretion system to modulate host cellular processes. Here we investigate the dynamics of subcellular structures containing ubiquitin during L. pneumophila infection of phagocytic host cells. The Dot/Icm system mediated the formation of K48 and K63 poly-ubiquitin conjugates to proteins associated with L. pneumophila-containing vacuoles in macrophages and dendritic cells, suggesting that regulatory events and degradative events involving ubiquitin are regulated by bacterial effectors during infection. Stimulation of TLR2 on the surface of macrophages and dendritic cells by L. pneumophila-derived molecules resulted in the production of ubiquitin-rich dendritic cell aggresome-like structures (DALIS). Cells infected by L. pneumophila with a functional Dot/Icm system, however, failed to produce DALIS. Suppression of DALIS formation did not affect the accumulation of ubiquitinated proteins on vacuoles containing L. pneumophila. Examining other species of Legionella revealed that L. jordanis was unable to suppress DALIS formation after creating a ubiquitin-decorated vacuole. Thus, the L. pneumophila Dot/Icm system has the ability to modulate host processes to promote K48 and K63 ubiquitin conjugates on proteins at the vacuole membrane, and independently suppress cellular events required for the formation of DALIS.
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DOI：
10.1084/jem.158.6.2108
发表时间：
1983-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horwitz MA
通讯作者：
Horwitz MA
DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
56.9
作者：
Nagai, H;Kagan, JC;Roy, CR
通讯作者：
Roy, CR
影响因子：
3.6
作者：
Kubori, Tomoko;Hyakutake, Akihiro;Nagai, Hiroki
通讯作者：
Nagai, Hiroki
影响因子：
64.8
作者：
Lelouard, H;Gatti, E;Pierre, P
通讯作者：
Pierre, P