Toxoplasma gondii Exploits the Host ESCRT Machinery for Parasite Uptake of Host Cytosolic Proteins

Yolanda Rivera-Cuevas, University, My
A variety of pathogens, from viruses to bacteria, have developed mechanisms to exploit the host endosomal sorting complex required for transport (ESCRT) machinery for intracellular subsistence and replication. Here, we elucidate the mechanism for host ESCRT recruitment to the replicative compartment of the obligate intracellular parasite Toxoplasma gondii. We discovered that this eukaryotic microorganism exploits the host ESCRT machinery for the uptake of host cytosolic proteins that are
more » ... to be a source of nutrients for the parasite. Furthermore, we have identified the parasite dense granule protein GRA14, which contains motifs homologous to the ESCRT-interacting late domain motifs of the HIV-1 Gag and is necessary for uptake of host cytosolic proteins, as an ESCRT-interacting parasite effector protein. GRA14 contributes to the recruitment of early- and late-acting ESCRT components such as TSG101 and VPS4B via its late domain motifs. Thus, as our working model we propose that host ESCRT components interact with GRA14 to trigger the formation of vesicles across the PV membrane (PVM) that contain host-derived resources. This work shed light on the first described mechanisms for ESCRT exploitation by a eukaryotic microorganism and provides evidence for a conserved role of the late domain, first described to be important in retroviral budding, in this process.
doi:10.7302/4747 fatcat:hpv7h2ufkfecff75phok2yvrvi