Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06526, USA.
Cell Host Microbe. 2012 Jan 19;11(1):46-57. doi: 10.1016/j.chom.2011.11.009.
The intracellular bacterial pathogen Legionella pneumophila subverts host membrane transport pathways to promote fusion of vesicles exiting the endoplasmic reticulum (ER) with the pathogen-containing vacuole. During infection there is noncanonical pairing of the SNARE protein Sec22b on ER-derived vesicles with plasma membrane (PM)-localized syntaxin proteins on the vacuole. We show that the L. pneumophila Rab1-targeting effector DrrA is sufficient to stimulate this noncanonical SNARE association and promote membrane fusion. DrrA activation of the Rab1 GTPase on PM-derived organelles stimulated the tethering of ER-derived vesicles with the PM-derived organelle, resulting in vesicle fusion through the pairing of Sec22b with the PM syntaxin proteins. Thus, the effector protein DrrA stimulates a host membrane transport pathway that enables ER-derived vesicles to remodel a PM-derived organelle, suggesting that Rab1 activation at the PM is sufficient to promote the recruitment and fusion of ER-derived vesicles.
细胞内细菌病原体军团菌（Legionella pneumophila）颠覆宿主膜运输途径，促进从内质网（ER）中离开的囊泡与包含病原体的空泡融合。在感染过程中，内质网来源的囊泡上的 SNARE 蛋白 Sec22b 与空泡上的质膜（PM）定位的突触蛋白发生非典型配对。我们表明，军团菌 Rab1 靶向效应蛋白 DrrA 足以刺激这种非典型 SNARE 关联并促进膜融合。DrrA 对 PM 衍生细胞器上 Rab1 GTPase 的激活刺激了内质网衍生囊泡与 PM 衍生细胞器的系留，导致囊泡通过 Sec22b 与 PM 突触蛋白的配对融合。因此，效应蛋白 DrrA 刺激宿主膜运输途径，使内质网衍生的囊泡能够重塑 PM 衍生的细胞器，这表明 PM 处的 Rab1 激活足以促进 ER 衍生囊泡的募集和融合。
