Transport mechanisms at the malaria parasite-host cell interface

Beck, Josh R.; Ho, Chi-Min

doi:10.1371/journal.ppat.1009394

Cited by 51 publications

(56 citation statements)

References 178 publications

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“…The trafficking route that targets PEXEL proteins post plasmepsin V cleavage from the ER to the PV has been enigmatic. Following arrival at the PV, it has not been clear how PEXEL proteins are selected for export by the PTEX from other PV-resident proteins [14, 50]. We have now presented three key findings to suggest that HSP101 may be the key component that mediates these two processes.…”

Section: Discussionmentioning

confidence: 92%

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell

Gabriela

Matthews

Boshoven

et al. 2021

Preprint

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Plasmodium falciparum exports ~10% of its proteome into its host erythrocyte to modify the host cell’s physiology. The Plasmodium export element (PEXEL) motif contained within the N-terminus of most exported proteins directs the trafficking of those proteins into the erythrocyte. To reach the host cell, the PEXEL motif of exported proteins are processed by the endoplasmic reticulum (ER) resident aspartyl protease plasmepsin V. Then, following secretion into the parasite-encasing parasitophorous vacuole, the mature exported protein must be unfolded and translocated across the parasitophorous vacuole membrane by the Plasmodium translocon of exported proteins (PTEX). PTEX is a protein-conducting channel consisting of the pore-forming protein EXP2, the protein unfoldase HSP101, and structural component PTEX150. The mechanism of how exported proteins are specifically trafficked from the parasite’s ER following PEXEL cleavage to PTEX complexes on the parasitophorous vacuole membrane is currently not understood. Here, we present evidence that EXP2 and PTEX150 form a stable subcomplex that facilitates HSP101 docking. We also demonstrate that HSP101 localises both within the parasitophorous vacuole and within the parasite’s ER throughout the ring and trophozoite stage of the parasite, coinciding with the timeframe of protein export. Interestingly, we found that HSP101 can form specific interactions with model PEXEL proteins in the parasite ER, irrespective of their PEXEL processing status. Collectively, our data suggest that HSP101 recognises and chaperones PEXEL proteins from the ER to the parasitophorous vacuole and given HSP101’s specificity for the EXP2-PTEX150 subcomplex, this provides a mechanism for how exported proteins are specifically targeted to PTEX for translocation into the erythrocyte.

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Section: Discussionmentioning

confidence: 92%

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell

Gabriela

Matthews

Boshoven

et al. 2021

Preprint

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“…Importantly, intracellular parasites may also rely to some extent on host-cell machinery for nutrient uptake. For example, glucose uptake to the benefit of the Plasmodium parasite within erythrocytes involves mainly uptake via the host glucose transporter glu1 at the erythrocyte surface and then parasite-specific transporters at the level of the PPM [ 128 ]. Intracellular parasites also acquire nutrients via endocytic-like pathways.…”

Section: The Niche and Feeding Strategies In Vegetative Stagesmentioning

confidence: 99%

Nutrient Acquisition and Attachment Strategies in Basal Lineages: A Tough Nut to Crack in the Evolutionary Puzzle of Apicomplexa

Valigurová

Florent

2021

Microorganisms

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Apicomplexa are unicellular eukaryotes that parasitise a wide spectrum of invertebrates and vertebrates, including humans. In their hosts, they occupy a variety of niches, from extracellular cavities (intestine, coelom) to epicellular and intracellular locations, depending on the species and/or developmental stages. During their evolution, Apicomplexa thus developed an exceptionally wide range of unique features to reach these diversified parasitic niches and to survive there, at least long enough to ensure their own transmission or that of their progeny. This review summarises the current state of knowledge on the attachment/invasive and nutrient uptake strategies displayed by apicomplexan parasites, focusing on trophozoite stages of their so far poorly studied basal representatives, which mostly parasitise invertebrate hosts. We describe their most important morphofunctional features, and where applicable, discuss existing major similarities and/or differences in the corresponding mechanisms, incomparably better described at the molecular level in the more advanced Apicomplexa species, of medical and veterinary significance, which mainly occupy intracellular niches in vertebrate hosts.

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“…As discussed above, PNEPs may go directly from the ER to the PV, whereas PEXEL containing proteins possibly process through the Golgi before arriving in the PV ( Figure 3 ). Thus, exported proteins destined for the erythrocyte also need to be translocated across the PVM after their arrival to the parasitophorous vacuole [ 132 , 154 ]. This translocation is accomplished by a large membrane complex called the Plasmodium translocon of exported proteins (PTEX) [ 154 , 155 ].…”

Section: Remodeling the Host Erythrocyte By The Malaria Parasitementioning

confidence: 99%

“…Thus, exported proteins destined for the erythrocyte also need to be translocated across the PVM after their arrival to the parasitophorous vacuole [ 132 , 154 ]. This translocation is accomplished by a large membrane complex called the Plasmodium translocon of exported proteins (PTEX) [ 154 , 155 ]. The three major proteins making up this complex are HSP101, PTEX150, and EXP2.…”

Section: Remodeling the Host Erythrocyte By The Malaria Parasitementioning

confidence: 99%

Unique Endomembrane Systems and Virulence in Pathogenic Protozoa

Wiser

2021

Life

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Virulence in pathogenic protozoa is often tied to secretory processes such as the expression of adhesins on parasite surfaces or the secretion of proteases to assisted in tissue invasion and other proteins to avoid the immune system. This review is a broad overview of the endomembrane systems of pathogenic protozoa with a focus on Giardia, Trichomonas, Entamoeba, kinetoplastids, and apicomplexans. The focus is on unique features of these protozoa and how these features relate to virulence. In general, the basic elements of the endocytic and exocytic pathways are present in all protozoa. Some of these elements, especially the endosomal compartments, have been repurposed by the various species and quite often the repurposing is associated with virulence. The Apicomplexa exhibit the most unique endomembrane systems. This includes unique secretory organelles that play a central role in interactions between parasite and host and are involved in the invasion of host cells. Furthermore, as intracellular parasites, the apicomplexans extensively modify their host cells through the secretion of proteins and other material into the host cell. This includes a unique targeting motif for proteins destined for the host cell. Most notable among the apicomplexans is the malaria parasite, which extensively modifies and exports numerous proteins into the host erythrocyte. These modifications of the host erythrocyte include the formation of unique membranes and structures in the host erythrocyte cytoplasm and on the erythrocyte membrane. The transport of parasite proteins to the host erythrocyte involves several unique mechanisms and components, as well as the generation of compartments within the erythrocyte that participate in extraparasite trafficking.

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Transport mechanisms at the malaria parasite-host cell interface

Cited by 51 publications

References 178 publications

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell

Nutrient Acquisition and Attachment Strategies in Basal Lineages: A Tough Nut to Crack in the Evolutionary Puzzle of Apicomplexa

Unique Endomembrane Systems and Virulence in Pathogenic Protozoa

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