Requirement for the Rac GTPage in Chlamydia trachomatis invasion of non-phagocytic cells
Requirement for the Rac GTPage in Chlamydia trachomatis invasion of non-phagocytic cells
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DOI：
10.1111/j.1398-9219.2004.00184.x
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发表时间：
2004-06-01
期刊：
影响因子：
4.5
通讯作者：
Hackstadt, T
中科院分区：
文献类型：
--
作者：
Carabeo, RA;Grieshaber, SS;Hackstadt, T
衣原体是革兰氏阴性专性细胞内病原体，进入细胞内环境对其生存和复制至关重要。为了达到这个目的，衣原体已经进化出非常有效的侵入非吞噬细胞的手段。为了阐明沙眼衣原体在入侵过程中所利用的宿主细胞机制，我们研究了Rho GT3家族成员在衣原体原体内化中的作用。在细胞表面上的结合的基本体，肌动蛋白被迅速招募到网站的内化。Rho GT3家族成员经常参与肌动蛋白的局部募集。梭菌毒素B是已知的Rac、Cdc 42和Rho GTP酶的酶抑制剂，其显著降低了HeLa细胞的衣原体侵袭。在HeLa细胞中的显性阴性结构的表达表明，衣原体摄取依赖于Rac，但不依赖于Cdc42或RhoA。发现Rac而不是Cdc42被衣原体附着激活。显性负性Rac表达对衣原体摄取的影响通过抑制肌动蛋白募集到衣原体进入的位点来表现。利用Rac、Cdc 42和RhoA的绿色荧光蛋白融合构建体的研究显示，Rac是被募集到衣原体进入位点的Rho GT3家族的唯一成员。
Chlamydiae are gram-negative obligate intracellular pathogens to which access to an intracellular environment is paramount to their survival and replication. To this end, chlamydiae have evolved extremely efficient means of invading nonphagocytic cells. To elucidate the host cell machinery utilized by Chlamydia trachomatis in invasion, we examined the roles of the Rho GTPase family members in the internalization of chlamydial elementary bodies. Upon binding of elementary bodies on the cell surface, actin is rapidly recruited to the sites of internalization. Members of the Rho GTPase family are frequently involved in localized recruitment of actin. Clostridial Toxin B, which is a known enzymatic inhibitor of Rac, Cdc42 and Rho GTPases, significantly reduced chlamydial invasion of HeLa cells. Expression of dominant negative constructs in HeLa cells revealed that chlamydial uptake was dependent on Rac, but not on Cdc42 or RhoA. Rac but not Cdc42 was found to be activated by chlamydial attachment. The effect of dominant negative Rac expression on chlamydial uptake is manifested through the inhibition of actin recruitment to the sites of chlamydial entry. Studies utilizing Green Fluorescent Protein fusion constructs of Rac, Cdc42 and RhoA, showed Rac to be the sole member of the Rho GTPase family recruited to the site of chlamydial entry.