Pfsbp1, a Maurer's cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton

Blisnick, Thierry; Betoulle, Maria Eugenia Morales; Barale, Jean-Christophe; Uzureau, Pierrick; Berry, Laurence; Desroses, Sarah; Fujioka, Hisashi; Mattei, Denise; Breton, Catherine Braun

doi:10.1016/s0166-6851(00)00301-7

Cited by 210 publications

(296 citation statements)

References 42 publications

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“…This orientation is similar to that of SBP1 (Blisnick et al, 2000), which we used as a control in this study. Using saponin instead of a harsher detergent in our proteinase K assay, we were able to selectively permeabilize the clefts and the PVM only.…”

Section: Discussionmentioning

confidence: 93%

“…Early transcribed membrane proteins (ETRAMPs) localize to the parasitophorous vacuole membrane (PVM), which surrounds the parasite inside the host cell (Spielmann et al, , 2006. Skeleton binding protein 1 (SBP1) and membrane-associated protein (MAHRP)1 localize to the Maurer's clefts (Blisnick et al, 2000;Spycher et al, 2003), parasite-induced vesicular structures in the host cell that are involved in the export of cytoadherence determinants to the RBC surface (Wickham et al, 2001;Knuepfer et al, 2005b). Interestingly, SBP1 has now been shown to be essential for export of PfEMP-1 to the RBC surface (Cooke et al, 2006).…”

mentioning

confidence: 99%

“…These results also confirmed that REX2 is an exported protein, because it otherwise would not have been accessible for digestion. To confirm the integrity of the clefts after SLO treatment and to check the completeness of the SLO lysis, extracts from each experiment were tested for the integral Maurer's cleft protein SBP1 (Blisnick et al, 2000). SBP1 is a single-pass transmembrane protein with its Cterminal region facing the RBC cytoplasm and its N terminus buried inside the clefts.…”

mentioning

confidence: 99%

“…The integral Maurer's cleft protein SBP1 served as a control for the integrity of the clefts and completeness of the SLO lysis. SBP1 is located in the Maurer's clefts membrane with its C terminus facing the red cell cytoplasm (Blisnick et al, 2000). Analysis of this protein in these samples showed that its C terminus was digested in the presence of proteinase K (using a serum against its C terminus) and that digestion left a smaller N-terminal fragment (using a serum against its N terminus) that was protected by the cleft membrane.…”

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confidence: 99%

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A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

Spielmann

Hawthorne

Dixon

et al. 2006

MBoC

117

162

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Blood stages of Plasmodium falciparum export proteins into their erythrocyte host, thereby inducing extensive host cell modifications that become apparent after the first half of the asexual development cycle (ring stage). This is responsible for a major part of parasite virulence. Export of many parasite proteins depends on a sequence motif termed Plasmodium export element (PEXEL) or vacuolar transport signal (VTS). This motif has allowed the prediction of the Plasmodium exportome. Using published genome sequence, we redetermined the boundaries of a previously studied region linked to P. falciparum virulence, reducing the number of candidate genes in this region to 13. Among these, we identified a cluster of four ring stage-specific genes, one of which is known to encode an exported protein. We demonstrate that all four genes code for proteins exported into the host cell, although only two genes contain an obvious PEXEL/VTS motif. We propose that the systematic analysis of ring stage-specific genes will reveal a cohort of exported proteins not present in the currently predicted exportome. Moreover, this provides further evidence that host cell remodeling is a major task of this developmental stage. Biochemical and photobleaching studies using these proteins reveal new properties of the parasiteinduced membrane compartments in the host cell. This has important implications for the biogenesis and connectivity of these structures. INTRODUCTIONPlasmodium falciparum is the causative agent of the most severe form of human malaria, killing 1-2 million people each year (Snow et al., 2005). The symptoms of this disease are associated with the continuous asexual multiplication of P. falciparum parasites within red blood cells (RBCs) (for review, see Miller et al., 2002). In this part of the life cycle, the parasite develops, within 48 h from the ring stage, to the trophozoite stage and finally to the schizont stage after which the infected RBCs (IRBCs) rupture, releasing up to 32 merozoite stage parasites that infect new RBCs.The ring stage lasts for almost half of this cycle (ϳ0-20 h after invasion) and shows low metabolic activity with little change in size and morphology (Zolg et al., 1984;de Rojas and Wasserman, 1985). P. falciparum ring forms are the only stages apparent in the blood circulation of infected humans, because more mature parasites adhere to the endothelium of various organs to avoid clearance by the spleen (Langreth and Peterson, 1985). The subsequent accumulation of infected RBCs in the microvasculature is largely responsible for malaria-associated morbidity and mortality. This sequestration of IRBCs is mediated by the parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP-1), which is exported to the surface of the IRBCs and is encoded by a family of variant antigens (Baruch et al., 1995;Smith et al., 1995;Su et al., 1995). Because human RBCs are devoid of a functional protein trafficking system, the parasite has to establish a protein export system in the host cell before PfEMP-1 can b...

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

Spielmann

Hawthorne

Dixon

et al. 2006

MBoC

117

162

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“…Others have shown that haptoglobin 2-2 and 2-1 cause agglutination of T4 Streptococcus pyogenes [7] but we have shown that haptoglobin does not cause agglutination of parasitised cells (unpublished observations). Haptoglobin is known to have a bacteriostatic effect on Escherischia coli due to its ability to bind hemoglobin [22] and thus it may affect the uptake of nutrients by P. falciparum in an analogous manner. P. falciparum produces complex membranous structures within the host cell cytoplasm, including flattened lamaellae called Maurer's clefts which are implicated in the transport of parasite proteins to the erythrocyte plasma membrane and submembrane skeleton [23].…”

Section: Discussionmentioning

confidence: 99%

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro

Imrie

Ferguson

Day

2004

Molecular and Biochemical Parasitology

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Innate immune responses are important in the control of malaria, particularly in those who have not yet mounted an effective adaptive response. Here we report that the human serum acute phase protein, haptoglobin is toxic to Plasmodium falciparum cultured in vitro. This effect is phenotype-dependent and occurs during the trophozoite phase of the asexual life cycle. We propose that the increased levels of haptoglobin seen in the acute phase response may be protective against malaria in humans.

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3‐D analysis of the Plasmodium falciparum Maurer's clefts using different electron tomographic approaches

Henrich

Kilian

Lanzer

et al. 2009

Biotechnology Journal

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The human malaria parasite Plasmodium falciparum exports a large number of proteins into its host erythrocyte to install functions necessary for parasite survival. Important structural components of the export machinery are membrane profiles of parasite origin, termed Maurer's clefts. These profiles span much of the distance between the parasite and the host cell periphery and are believed to deliver P. falciparum-encoded proteins to the erythrocyte plasma membrane. Although discovered more than a century ago, Maurer's clefts remain a mysterious organelle with little information available regarding their origin, their morphology or their precise role in protein trafficking. Here, we evaluated different techniques to prepare samples for electron tomography, including whole cell cryo-preparations, vitreous sections, freeze-substitution and chemical fixation. Our data show that the different approaches tested all have their merits, revealing different aspects of the complex structure of the Maurer's clefts.

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Pfsbp1, a Maurer's cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton

Cited by 210 publications

References 42 publications

A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro

3‐D analysis of the Plasmodium falciparum Maurer's clefts using different electron tomographic approaches

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