Apicomplexan parasites possess secretory organelles called rhoptries that undergo regulated exocytosis upon contact with the host. This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. However, how the parasites coordinate exocytosis with host interaction is unknown. Here, we performed a Tetrahymena-based transcriptomic screen to uncover novel exocytic factors in Ciliata and conserved in Apicomplexa. We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. Using cutting-edge imaging tools, including expansion microscopy and cryo-electron tomography, we show that, unlike previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery and only transiently associate with the exocytic site—prior to the invasion. CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarities with GPCR proteins. Collectively our data imply that the CRMP complex acts as a host–molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell.

中文翻译：

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一种在弓形虫中触发菱形胞吐和入侵的顶膜复合物

Apicomplexan 寄生虫拥有称为 rhoptries 的分泌细胞器，在与宿主接触时会发生受调节的胞吐作用。这个过程对于这些病原体的寄生生活方式至关重要，并且依赖于与自由生活的纤毛虫共享结构特征和分子成分的胞吐机制。然而，寄生虫如何协调胞吐作用与宿主相互作用尚不清楚。在这里，我们进行了基于四膜虫的转录组学筛选，以发现纤毛虫中新的胞吐因子并在顶复门中保存。我们确定了称为 CRMP 的膜结合蛋白，它是弓形虫中菱形分泌和入侵所必需的大型复合体的一部分. 使用尖端成像工具，包括膨胀显微镜和冷冻电子断层扫描，我们表明，与之前描述的菱形胞吐因子不同，TgCRMP 不需要菱形分泌机制的组装，并且仅在入侵。CRMP 及其伙伴包含假定的宿主细胞结合域，并且 CRMPa 与 GPCR 蛋白有相似之处。总的来说，我们的数据表明 CRMP 复合物充当宿主 - 分子传感器，以确保当寄生虫接触宿主细胞时发生菱形胞吐作用。