Abstract
Apicomplexans form a large phylum of parasitic protozoa, including the genera Plasmodium, Toxoplasma, and Cryptosporidium, the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively. They cause diseases not only in humans but also in animals, with dramatic consequences in agriculture. Most apicomplexans are vacuole-dwelling and obligate intracellular parasites; as they invade the host cell, they become encased in a parasitophorous vacuole (PV) derived from the host cellular membrane. This creates a parasite–host interface that acts as a protective barrier but also constitutes an obstacle through which the pathogen must import nutrients, eliminate wastes, and eventually break free upon egress. Completion of the parasitic life cycle requires intense remodeling of the infected host cell. Host cell subversion is mediated by a subset of essential effector parasitic proteins and virulence factors actively trafficked across the PV membrane. In the malaria parasite Plasmodium, a unique and highly specialized ATP-driven vacuolar secretion system, the Plasmodium translocon of exported proteins (PTEX), transports effector proteins across the vacuolar membrane. Its core is composed of the three essential proteins EXP2, PTEX150, and HSP101, and is supplemented by the two auxiliary proteins TRX2 and PTEX88. Many but not all secreted malarial effector proteins contain a vacuolar trafficking signal or Plasmodium export element (PEXEL) that requires processing by an endoplasmic reticulum protease, plasmepsin V, for proper export. Because vacuolar parasitic protein export is essential to parasite survival and virulence, this pathway is a promising target for the development of novel antimalarial therapeutics. This review summarizes the current state of structural and mechanistic knowledge on the Plasmodium parasitic vacuolar secretion and effector trafficking pathway, describing its most salient features and discussing the existing differences and commonalities with the vacuolar effector translocation MYR machinery recently described in Toxoplasma and other apicomplexans of significance to medical and veterinary sciences.
Highlights
Apicomplexa form a large group of parasitic protozoa and are characterized by the presence of complex apical ultra-structures and a unique plastid-like organelle, the apicoplast, product of an ancient endosymbiotic event between a photosynthetic protist and a heterotrophic ancestor cell [1,2]
We do not yet understand in what state(s) proteins destined for insertion inside the PV membrane (PVM) or translocation across the PVM are delivered to the membrane or PTEX, respectively
Proteins are maintained in an unfolded state presumably associated with chaperones but the molecular machineries involved in these steps remain largely unknown
Summary
Apicomplexa form a large group of parasitic protozoa and are characterized by the presence of complex apical ultra-structures and a unique plastid-like organelle, the apicoplast, product of an ancient endosymbiotic event between a photosynthetic protist (red alga) and a heterotrophic ancestor cell [1,2]. In the last two decades, our understanding of the mechanisms underlying apicomplexan pathogenicity and virulence at the level of molecular structures seen at atomic resolution has dramatically expanded This large body of knowledge only relates to Plasmodium and Toxoplasma. Plasmodium and Toxoplasma extensively remodel their respective host cells via secreted effector proteins, which they introduce during or following invasion [5,6,7,8]. A cornucopia of effector proteins and virulence factors are trafficked into and across the parasitophorous vacuole (PV) to subvert the host cell and successfully mount a cyclic (Plasmodium) or latent/chronic (Toxoplasma) infection. The Plasmodium translocon of exported proteins (PTEX) [9] and the MYR protein complex (for host c-Myc regulation) [10] in Toxoplasma, have been identified. This provided some mechanistic insights into effector translocation across the PVM by this unique translocon
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
