Illuminating how malaria parasites export proteins into host erythrocytes

Matthews, Kathryn; Pitman, Ethan L; Koning-Ward, Tania F. de

doi:10.1111/cmi.13009

Cited by 32 publications

(28 citation statements)

References 71 publications

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“…After invasion, the parasite exports hundreds of proteins into the host RBC. These exported effectors enact a dramatic program of host modification, reconstituting a complex trafficking system in the RBC cytosol and altering the host cell's rigidity, nutrient permeability, and endothelial binding properties (98,99). A significant portion of this export program appears dedicated to trafficking families of variable membrane adhesins to the RBC surface, creating adhesin-rich protrusions called "knobs" that mediate binding to the vascular endothelium ( Fig.…”

Section: Key Questionsmentioning

confidence: 99%

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Nasamu¹,

Polino²,

Istvan

et al. 2020

Journal of Biological Chemistry

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Plasmepsins are a group of diverse aspartic proteases in the malaria parasite Plasmodium. Their functions are strikingly multifaceted, ranging from hemoglobin degradation to secretory organelle protein processing for egress, invasion, and effector export. Some, particularly the digestive vacuole plasmepsins, have been extensively characterized, whereas others, such as the transmission-stage plasmepsins, are minimally understood. Some (e.g. plasmepsin V) have exquisite cleavage sequence specificity; others are fairly promiscuous. Some have canonical pepsin-like aspartic protease features, whereas others have unusual attributes, including the nepenthesin loop of plasmepsin V and a histidine in place of a catalytic aspartate in plasmepsin III. We have learned much about the functioning of these enzymes, but more remains to be discovered about their cellular roles and even their mechanisms of action. Their importance in many key aspects of parasite biology makes them intriguing targets for antimalarial chemotherapy. Further consideration of their characteristics suggests that some are more viable drug targets than others. Indeed, inhibitors of invasion and egress offer hope for a desperately needed new drug to combat this nefarious organism.

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Section: Key Questionsmentioning

confidence: 99%

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Nasamu¹,

Polino²,

Istvan

et al. 2020

Journal of Biological Chemistry

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“…Because the fungal haustorium cell is accommodated inside the plant cell, it is assumed that the majority of the proteins secreted by fungal haustorium are either hosttranslocated or function at the EHMX. The translocation of effectors through the haustorial interface could possibly occur by (1) receptor-mediated endocytosis, (2) fusion of EVs loaded with effectors, or (3) through active transport facilitated by a pathogenencoded translocon (see poster), as is the case in the apicomplexan parasite Plasmodium (Matthews et al, 2019).…”

Section: Molecular Traffic Across the Haustorial Interfacementioning

confidence: 99%

The plant–pathogen haustorial interface at a glance

Bozkurt

Kamoun

2020

Journal of Cell Science

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Many filamentous pathogens invade plant cells through specialized hyphae called haustoria. These infection structures are enveloped by a newly synthesized plant-derived membrane called the extrahaustorial membrane (EHM). This specialized membrane is the ultimate interface between the plant and pathogen, and is key to the success or failure of infection. Strikingly, the EHM is reminiscent of host-derived membrane interfaces that engulf intracellular metazoan parasites. These perimicrobial interfaces are critical sites where pathogens facilitate nutrient uptake and deploy virulence factors to disarm cellular defenses mounted by their hosts. Although the mechanisms underlying the biogenesis and functions of these host-microbe interfaces are poorly understood, recent studies have provided new insights into the cellular and molecular mechanisms involved. In this Cell Science at a Glance and the accompanying poster, we summarize these recent advances with a specific focus on the haustorial interfaces associated with filamentous plant pathogens. We highlight the progress in the field that fundamentally underpin this research topic. Furthermore, we relate our knowledge of plant-filamentous pathogen interfaces to those generated by other plant-associated organisms. Finally, we compare the similarities between host-pathogen interfaces in plants and animals, and emphasize the key questions in this research area.

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“…In the related Plasmodium parasites, a system for translocation across the PVM has been well characterized and is commonly referred to as PTEX for “ Plasmodium translocon of exported proteins” (Ho et al., 2018). As the name implies, PTEX includes a translocon, chaperone, and other associated proteins (Matthews et al., 2019). As with GRA16, licensing of exported proteins for translocation appears dependent on cleavage by the Plasmodium equivalent of ASP5, albeit within the parasite's endoplasmic reticulum rather than within the Golgi used by Toxoplasma .…”

Section: Translocation Of Gra Effectors Across the Pvm Is Mediated Bymentioning

confidence: 99%

Seizing control: How dense granule effector proteins enable Toxoplasma to take charge

Panas

Boothroyd

2021

Molecular Microbiology

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Control of the host cell is crucial to the Apicomplexan parasite, Toxoplasma gondii, while it grows intracellularly. To achieve this goal, these single-celled eukaryotes export a series of effector proteins from organelles known as "dense granules" that interfere with normal cellular processes and responses to invasion. While some effectors are found attached to the outer surface of the parasitophorous vacuole (PV) in which Toxoplasma tachyzoites reside, others are found in the host cell's cytoplasm and yet others make their way into the host nucleus, where they alter host transcription. Among the processes that are severely altered are innate immune responses, host cell cycle, and association with host organelles. The ways in which these crucial processes are altered through the coordinated action of a large collection of effectors is as elegant as it is complex, and is the central focus of the following review; we also discuss the recent advances in our understanding of how dense granule effector proteins are trafficked out of the PV. K E Y W O R D Sdense granule, effector protein, innate immunity, toxoplasma | 467 PANAS ANd BOOTHROYd Effector Host cell location Summary of function MYR-dependent GRA16 Nucleus Binds HAUSP, PP2AB55, leads to c-Myc induction, p53 activation, cyclin A degradation, alterations in sterol pathways GRA18 Cytoplasm Binds B-catenin degradation complex preventing B-catenin degradation, upregulates CCL17 and CCL22 GRA24 Nucleus Binds and triggers autophosphorylation of p38 MAPkinase, triggering cytokine production GRA28 Nucleus Upregulates CCL22 HCE1/TEEGR Nucleus Binds to E2F3/4, upregulates cell cycle genes, reduces chromatin access, limits cytokine production TgIST Nucleus Binds STAT1 and Mi2-NuRD complex silencing IGNg responses.

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Illuminating how malaria parasites export proteins into host erythrocytes

Cited by 32 publications

References 71 publications

Malaria parasite plasmepsins: More than just plain old degradative pepsins

Malaria parasite plasmepsins: More than just plain old degradative pepsins

The plant–pathogen haustorial interface at a glance

Seizing control: How dense granule effector proteins enable Toxoplasma to take charge

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