Mona Höhler, Abel R Alcázar-Román, Katharina Schenk, Mac Pholo Aguirre-Huamani, Corinna Braun, Rafat Zrieq, Katja Mölleken, Johannes H Hegemann, Ursula Fleig
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引用次数: 0
摘要
为了在真核细胞内繁殖,致病细菌会劫持和重塑宿主细胞的功能。对人类和动物健康构成严重威胁的革兰氏阴性细胞内衣原体,会附着在宿主细胞上并注入效应蛋白,对宿主细胞机制进行重编程。保守的衣原体 TarP 家族成员已被鉴定为主要的早期效应蛋白,可与宿主肌动蛋白细胞骨架结合并重塑其结构。我们现在描述了肺炎衣原体 TarP 成员 CPn0572 的一种新功能,即结合和改变微管细胞骨架的能力。因此,CPn0572 是唯一能直接调节真核细胞两种动态细胞骨架的原核蛋白质。异位表达的 GFP-CPn0572 能以剂量无关的方式单独或同时与两种细胞骨架结合。在体外,CPn0572 直接与微管结合。只表达微管的 CPn0572 变体会形成异常粗大、稳定的微管网络。有趣的是,在感染过程中,分泌的 CPn0572 也与改变的微管共定位,这表明该蛋白在感染过程中也会影响微管动力学。我们的分析表明,肌动蛋白和微管细胞骨架之间通过衣原体 CPn0572 产生了串扰。
Direct targeting of host microtubule and actin cytoskeletons by a chlamydial pathogenic effector protein.
To propagate within a eukaryotic cell, pathogenic bacteria hijack and remodulate host cell functions. The Gram-negative obligate intracellular Chlamydiaceae, which pose a serious threat to human and animal health, attach to host cells and inject effector proteins that reprogram host cell machineries. Members of the conserved chlamydial TarP family have been characterized as major early effectors that bind to and remodel the host actin cytoskeleton. We now describe a new function for the Chlamydia pneumoniae TarP member CPn0572, namely the ability to bind and alter the microtubule cytoskeleton. Thus, CPn0572 is unique in being the only prokaryotic protein that directly modulates both dynamic cytoskeletons of a eukaryotic cell. Ectopically expressed GFP-CPn0572 associates in a dose-independent manner with either cytoskeleton singly or simultaneously. In vitro, CPn0572 binds directly to microtubules. Expression of a microtubule-only CPn0572 variant resulted in the formation of an aberrantly thick, stabilized microtubule network. Intriguingly, during infection, secreted CPn0572 also colocalized with altered microtubules, suggesting that this protein also affects microtubule dynamics during infection. Our analysis points to a crosstalk between actin and microtubule cytoskeletons via chlamydial CPn0572.