Institute for Advanced Biosciences (IAB), Team Membrane Dynamics of Parasite-Host Cell Interactions, CNRS UMR5309, INSERM U1209, Université Grenoble Alpes, Grenoble 38700, France.
Unit of Malaria Infection and Immunity, Department of Parasites and Insect Vectors, Institut Pasteur, Paris 75015, France.
Cell Host Microbe. 2018 Jul 11;24(1):81-96.e5. doi: 10.1016/j.chom.2018.06.003. Epub 2018 Jun 28.
To invade cells, the parasite Toxoplasma gondii injects a multi-unit nanodevice into the target cell plasma membrane (PM). The core nanodevice, which is composed of the RhOptry Neck (RON) protein complex, connects Toxoplasma and host cell through a circular tight junction (TJ). We now report that this RON nanodevice mechanically promotes membrane scission at the TJ-PM interface, directing a physical rotation driven by the parasite twisting motion that enables the budding parasitophorous vacuole (PV) to seal and separate from the host cell PM as a bona fide subcellular Toxoplasma-loaded PV. Mechanically impairing the process induces swelling of the budding PV and death of the parasite but not host cell. Moreover, this study reveals that the parasite nanodevice functions as a molecular trigger to promote PV membrane remodeling and rapid onset of T. gondii to intracellular lifestyle.
为了入侵细胞，寄生虫刚地弓形虫将一个多单位纳米装置注入靶细胞的质膜 (PM)。该核心纳米装置由 RhOptry Neck (RON) 蛋白复合物组成，通过圆形紧密连接 (TJ) 将刚地弓形虫与宿主细胞连接起来。我们现在报告说，这个 RON 纳米装置在 TJ-PM 界面处机械促进膜分裂，通过寄生虫扭转运动驱动物理旋转，从而使萌芽的滋养液泡 (PV) 能够密封并与宿主细胞 PM 分离，成为真正的亚细胞负载刚地弓形虫的 PV。机械性地破坏这个过程会导致萌芽 PV 的肿胀和寄生虫的死亡，但不会导致宿主细胞的死亡。此外，这项研究揭示了寄生虫纳米装置作为一种分子触发因素，促进 PV 膜重塑，并使刚地弓形虫迅速进入细胞内生活方式。
