Chlamydia trachomatis uses host cell dynein to traffic to the microtubule-organizing center in a p50 dynamitin-independent process

被引:143
作者
Grieshaber, SS [1 ]
Grieshaber, NA [1 ]
Hackstadt, T [1 ]
机构
[1] NIAID, Rocky Mt Lab, Lab Intracellular Parasites, Host Parasite Interact Sect,NIH, Hamilton, MT 59840 USA
关键词
Chlamydia; cytoskeleton; Microtubules; dynein; dynactin;
D O I
10.1242/jcs.00695
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chlamydiae are pathogenic obligate intracellular bacteria with a biphasic developmental cycle that involves cell types adapted for extracellular survival (elementary bodies, EBs) and intracellular multiplication (reticulate bodies, RBs). The intracellular development of chlamydiae occurs entirely within a membrane-bound vacuole termed an inclusion. Within 2 hours after entry into host cells, Chlamydia trachomatis EBs are trafficked to the perinuclear region of the host cell and remain in close proximity to the Golgi apparatus, where they begin to fuse with a subset of host vesicles containing sphingomyelin. Here, we provide evidence that chlamydial migration from the cell periphery to the peri-Golgi region resembles host cell vesicular trafficking. Chlamydiae move towards the minus end of microtubules and aggregate at the microtubule-organizing center (MTOC). In mammalian cells the most important minus-end-directed microtubule motor is cytoplasmic dynein. Microinjection of antibodies to a subunit of cytoplasmic dynein inhibited movement of chlamydiae to the MTOC, whereas microinjection of antibodies to the plus-directed microtubule motor, kinesin, had no effect. Surprisingly, overexpression of the protein p50 dynamitin, a subunit of the dynactin complex that links vesicular cargo to the dynein motor in minus directed vesicle trafficking, did not abrogate chlamydial migration even though host vesicle transport was inhibited. Nascent chlamydial inclusions did, however, colocalize with the P150((Glued)) dynactin subunit, which suggests that p150((Glued)) may be required for dynein activation or processivity but that the cargo-binding activity of dynactin, supplied by p50 dynamitin subunits and possibly other subunits, is not. Because chlamydial transcription and translation were required for this intracellular trafficking, chlamydial proteins modifying the cytoplasmic face of the inclusion membrane are probable candidates for proteins fulfilling this function.
引用
收藏
页码:3793 / 3802
页数:10
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