Maurer's clefts, the enigma of
            <i>Plasmodium falciparum</i>

Mundwiler-Pachlatko, Esther; Beck, Hans‐Peter

doi:10.1073/pnas.1309247110

Cited by 106 publications

(87 citation statements)

References 119 publications

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“…Because PfPMV has a unique substrate specificity [6], the remaining but functionally uncharacterized PfPMX and PfPMIX enzymes [25] are now at the top of the list as possible targets for HIV PIs in malaria. These 'late' plasmepsins are expressed before parasite egression and are localized to the peripheral parts of the host secretory machinery -Maurer's clefts of infected erythrocytes [26]. They have also been found to interact with P. falciparum proteins that are known to localize to the host erythrocyte cytoplasm [27].…”

Section: Plasmodium Falciparummentioning

confidence: 99%

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Sojka

Hartmann

Bartošová-Sojková

et al. 2016

Trends in Parasitology

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Section: Plasmodium Falciparummentioning

confidence: 99%

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Sojka

Hartmann

Bartošová-Sojková

et al. 2016

Trends in Parasitology

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“…One of these membranous compartments is the parasitophorous vacuole membrane that surrounds the parasite during the entire intraerythrocytic life cycle and that separates the parasite from the erythrocyte cytosol. Another group of membranous compartments is the Maurer's clefts, small vesicles that are important for the transfer of parasite proteins to the surface of the infected cell (26, 27). As mature erythrocytes are devoid of internal membranes and lack the capacity to produce membranes (28), these newly formed membranes, which are all outside of and unconnected to the parasite, must be produced by the parasite.…”

Section: Introductionmentioning

confidence: 99%

Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites

Hill

Ringel

Knuepfer

et al. 2016

Journal of Biological Chemistry

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StAR-related lipid transfer (START) domains are phospholipid- or sterol-binding modules that are present in many proteins. START domain-containing proteins (START proteins) play important functions in eukaryotic cells, including the redistribution of phospholipids to subcellular compartments and delivering sterols to the mitochondrion for steroid synthesis. How the activity of the START domain is regulated remains unknown for most of these proteins. The Plasmodium falciparum START protein PFA0210c (PF3D7_0104200) is a broad-spectrum phospholipid transfer protein that is conserved in all sequenced Plasmodium species and is most closely related to the mammalian START proteins STARD2 and STARD7. PFA0210c is unusual in that it contains a signal sequence and a PEXEL export motif that together mediate transfer of the protein from the parasite to the host erythrocyte. The protein also contains a C-terminal extension, which is very uncommon among mammalian START proteins. Whereas the biochemical properties of PFA0210c have been characterized, the function of the protein remains unknown. Here, we provide evidence that the unusual C-terminal extension negatively regulates phospholipid transfer activity. Furthermore, we use the genetically tractable Plasmodium knowlesi model and recently developed genetic technology in P. falciparum to show that the protein is essential for growth of the parasite during the clinically relevant asexual blood stage life cycle. Finally, we show that the regulation of phospholipid transfer by PFA0210c is required in vivo, and we identify a potential second regulatory domain. These findings provide insight into a novel mechanism of regulation of phospholipid transfer in vivo and may have important implications for the interaction of the malaria parasite with its host cell.

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“…We and others have previously shown that a parasite-encoded protein, skeleton-binding protein 1 (SBP1), is essential for trafficking and translocation of PfEMP1 onto the RBC surface and consequently for adhesion of PRBCs to the vascular endothelium [10,11]. SBP1 is a trans-membrane protein, located in parasite-induced membranous structures within the PRBC cytoplasm known as Maurer's clefts (MCs) [12,13]. The topology of SBP1 is such that its entire N-terminal domain (SBP1-N; Fig.…”

Section: Introductionmentioning

confidence: 99%

Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells

Kats

Proellocks

Buckingham

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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During development inside red blood cells (RBCs), Plasmodium falciparum malaria parasites export proteins that associate with the RBC membrane skeleton. These interactions cause profound changes to the biophysical properties of RBCs that underpin the often severe and fatal clinical manifestations of falciparum malaria. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is one such exported parasite protein that plays a major role in malaria pathogenesis since its exposure on the parasitised RBC surface mediates their adhesion to vascular endothelium and placental syncytioblasts. En route to the RBC membrane skeleton, PfEMP1 transiently associates with Maurer's clefts (MCs), parasite-derived membranous structures in the RBC cytoplasm. We have previously shown that a resident MC protein, skeleton-binding protein 1 (SBP1), is essential for the placement of PfEMP1 onto the RBC surface and hypothesised that the function of SBP1 may be to target MCs to the RBC membrane. Since this would require additional protein interactions, we set out to identify binding partners for SBP1. Using a combination of approaches, we have defined the region of SBP1 that binds specifically to defined subdomains of two major components of the RBC membrane skeleton, protein 4.1R and spectrin. We show that these interactions serve as one mechanism to anchor MCs to the RBC membrane skeleton, however, while they appear to be necessary, they are not sufficient for the translocation of PfEMP1 onto the RBC surface. The N-terminal domain of SBP1 that resides within the lumen of MCs clearly plays an essential, but presently unknown role in this process.

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Maurer's clefts, the enigma of Plasmodium falciparum

Cited by 106 publications

References 119 publications

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites

Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells

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