Evidence for vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected ertythrocytes

Trelka, Darin; Schneider, Timothy; Reeder, John C.; Taraschi, Theodore F.

doi:10.1016/s0166-6851(99)00207-8

Cited by 84 publications

(78 citation statements)

References 47 publications

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“…PfPTP1 and SBP1 occur on these structures and it has been shown that PfEMP1 is found on structures with very similar characteristics. 23,26 Models have been suggested for trafficking PfEMP1 to MC and its final destination on the P falciparum-infected RBC surface including: (1) loading of PfEMP1 onto nascent MC as they bud from the PVM, (2) transport in vesicles to MC, 24 (3) transport as soluble complexes that insert into fully formed MC. 10,29 Recent studies show MC bud from the PVM and establish in the RBC cytoplasm after invasion before expression of proteins normally resident in or traveling through these organelles, including PfEMP1.…”

Section: Discussionmentioning

confidence: 99%

“…5 It has been suggested that PfEMP1 trafficking from the MC to the RBC membrane occurs through vesicular transport \along actin filaments. [24][25][26] There are a number of different vesicles described in P falciparum including electron dense vesicles (EDVs), J-dots, and vesicle-like structures (VLSs), which could play a role in PfEMP1 trafficking. [27][28][29][30][31] We have characterized a novel PEXEL-containing protein that we have named P falciparum PfEMP1 trafficking protein.…”

Section: Introductionmentioning

confidence: 99%

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Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

Rug

Cyrklaff

Mikkonen

et al. 2014

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

Rug

Cyrklaff

Mikkonen

et al. 2014

Blood

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“…Immunofluorescence and immunoelectron microscopy (EM) studies indicate that plasmodial homologs of the coat proteins, Sar1p, Sec31p, and Sec23p, are exported to the host RBC cytoplasm, where they are associated with structures known as the Maurer's clefts (1,4,65,68,69). Moreover small vesicles, potentially involved in trafficking from the parasitophorous vacuole membrane to the host cell membrane, have been visualized in the RBC cytosol (65,66).…”

mentioning

confidence: 99%

Delivery of the Malaria Virulence Protein PfEMP1 to the Erythrocyte Surface Requires Cholesterol-Rich Domains

Frankland

Adisa²,

Horrocks

et al. 2006

Eukaryot Cell

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The particular virulence of the human malaria parasite Plasmodium falciparum derives from export of parasite-encoded proteins to the surface of the mature erythrocytes in which it resides. The mechanisms and machinery for the export of proteins to the erythrocyte membrane are largely unknown. In other eukaryotic cells, cholesterol-rich membrane microdomains or "rafts" have been shown to play an important role in the export of proteins to the cell surface. Our data suggest that depletion of cholesterol from the erythrocyte membrane with methyl-␤-cyclodextrin significantly inhibits the delivery of the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). The trafficking defect appears to lie at the level of transfer of PfEMP1 from parasite-derived membranous structures within the infected erythrocyte cytoplasm, known as the Maurer's clefts, to the erythrocyte membrane. Thus our data suggest that delivery of this key cytoadherence-mediating protein to the host erythrocyte membrane involves insertion of PfEMP1 at cholesterol-rich microdomains. GTP-dependent vesicle budding and fusion events are also involved in many trafficking processes. To determine whether GTP-dependent events are involved in PfEMP1 trafficking, we have incorporated non-membrane-permeating GTP analogs inside resealed erythrocytes. Although these nonhydrolyzable GTP analogs reduced erythrocyte invasion efficiency and partially retarded growth of the intracellular parasite, they appeared to have little direct effect on PfEMP1 trafficking.

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“…Trelka et al showed strings of vesicles (116), and those associated with Maurer's clefts had a diameter of about 25 nm (21, 24, 31, 36), but a few larger vesicles of about 80 nm in diameter with an electrondense coat around a lumen of approximately 25 nm were also found in trophozoiteinfected erythrocytes and were called electron-dense vesicles (36,45,116). These vesicles share morphological features with the knob complex, but are both present in knob-carrying and knobless infected erythrocytes (36).…”

Section: Proteins Reach Maurer's Clefts Via a Complex Transport Pathwaymentioning

confidence: 99%

Maurer's clefts, the enigma of Plasmodium falciparum

Mundwiler-Pachlatko

Beck

2013

Proc. Natl. Acad. Sci. U.S.A.

101

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Plasmodium falciparum, the causative agent of malaria, completely remodels the infected human erythrocyte to acquire nutrients and to evade the immune system. For this process, the parasite exports more than 10% of all its proteins into the host cell cytosol, including the major virulence factor PfEMP1 (P. falciparum erythrocyte surface protein 1). This unusual protein trafficking system involves long-known parasitederived membranous structures in the host cell cytosol, called Maurer's clefts. However, the genesis, role, and function of Maurer's clefts remain elusive. Similarly unclear is how proteins are sorted and how they are transported to and from these structures. Recent years have seen a large increase of knowledge but, as yet, no functional model has been established. In this perspective we review the most important findings and conclude with potential possibilities to shed light into the enigma of Maurer's clefts. Understanding the mechanism and function of these structures, as well as their involvement in protein export in P. falciparum, might lead to innovative control strategies and might give us a handle with which to help to eliminate this deadly parasite.

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Evidence for vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected ertythrocytes

Cited by 84 publications

References 47 publications

Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

Delivery of the Malaria Virulence Protein PfEMP1 to the Erythrocyte Surface Requires Cholesterol-Rich Domains

Maurer's clefts, the enigma of Plasmodium falciparum

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