An apical membrane complex for triggering rhoptry exocytosis and invasion in Toxoplasma

Abstract

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. image Surface‐exposed cysteine repeat modular proteins (CRMPs) are required for the Plasmodium parasite targeting the mosquito salivary gland. Here, CRMPs are shown to be essential for rhoptry secretion and host invasion in Toxoplasma gondii , potentially by acting as molecular sensors of host cell contact. Tetrahymena ‐based transcriptomic screening identifies CRMP homologs as new factors essential for regulated exocytosis. CRMP homologs in Toxoplasma are part of a large complex essential for rhoptry secretion and host invasion. The CRMP complex translocates near the rhoptry exocytic site at the time of invasion but is dispensable for the positioning of the rhoptry exocytic machinery. TgCRMPa bears features of GPCR receptors and an N‐terminus that is exposed to the extracellular space.