Identification of peripheral membrane proteins associated with the tubo-vesicular network of Plasmodium falciparum infected erythrocytes

Martı́nez, Servet; Clavijo, Carlos; Winograd, Enrique

doi:10.1016/s0166-6851(97)00206-5

Cited by 24 publications

(23 citation statements)

References 23 publications

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“…Indeed, the compact curling might be hampered by structures remaining attached to the iRBC membrane after egress such as the submembrane skeleton and the Maurer clefts, previously shown to remain attached to the RBC membrane after egress. [20][21][22][23] Moreover, studying the curling in a viscous fluid of an elastic stripe, with a spontaneous curvature, we observed that viscous friction prevents a compact curling as shown and discussed in the supplemental Figure 1A. The full description of such experiments is out of the scope of this article and this process is currently further investigated.…”

Section: Malaria Egress From Erythrocytes 4121mentioning

confidence: 65%

“…Importantly, the parasite induces modifications of the RBC membrane and submembrane skeleton and links the Maurer clefts to the iRBC membrane from Ͻ 2 hours postinvasion up to merozoite release. [20][21][22][23] Therefore, efficient egress of the merozoites might involve the release of interactions between the lipid membrane and these underlying structures. 29 Thus, unzipping the RBC membrane from these structures could account for such a high effective viscosity eff and proteolytic activities reported to be crucial for release 3,30-32 might be implicated.…”

Section: Malaria Egress From Erythrocytes 4121mentioning

confidence: 99%

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A novel mechanism for egress of malarial parasites from red blood cells

Abkarian

Massiera

Berry

et al. 2011

Blood

123

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The culminating step of the intraerythrocytic development of Plasmodium falciparum, the causative agent of malaria, is the spectacular release of multiple invasive merozoites on rupture of the infected erythrocyte membrane. This work reports for the first time that the whole process, taking place in time scales as short as 400 milliseconds, is the result of an elastic instability of the infected erythrocyte membrane. Using high-speed differential interference contrast (DIC) video microscopy and epifluorescence, we demonstrate that the release occurs in 3 main steps after osmotic swelling of the infected erythrocyte: a pore opens in ϳ 100 milliseconds, ejecting 1-2 merozoites, an outward curling of the erythrocyte membrane is then observed, ending with a fast eversion of the infected erythrocyte membrane, pushing the parasites forward. It is noteworthy that this last step shows slight differences when infected erythrocytes are adhering. We rationalize our observations by considering that during the parasite development, the infected erythrocyte membrane acquires a spontaneous curvature and we present a subsequent model describing the dynamics of the curling rim. Our results show that sequential erythrocyte membrane curling and eversion is necessary for the parasite efficient angular dispersion and might be biologically essential for fast and numerous invasions of new erythrocytes. (Blood. 2011;117(15):4118-4124) IntroductionThe phylum Apicomplexa includes a large number of notorious human and animal pathogens such as Plasmodium falciparum, the causative agent of severe cases of malaria, killing millions of people every year and reported to be clinically responsible for death since Pharaon times. 1 Host cell invasion by these obligate intracellular parasites occurs by active penetration of the host cell with the formation of a parasitophorous vacuole (PV). All along the erythrocytic cycle, and to achieve the needs of their growth, multiplication, and final release, Plasmodium parasites highly modify both the host cell membrane and their PV. Newly formed invasive parasites then escape from the host cell after the sequential opening of the PV and the host RBC membranes. 2 Although some parasite proteins, and particularly a cascade of proteolytic activities, 3 have been shown to be implicated, the dynamics of merozoite release, the crucial and very last step of the parasite intraerythrocytic development, and its mechanisms still remain to be deciphered. 4 It is still commonly referred to as an "explosive" event, 2,5,6 35 years after the seminal video microscopy work of Dvorak et al. 7 However, what happens to the membrane during this "explosion" and, in particular, how parasite displacements can reach several times the parasite body size in a split second without any swimming appendices or inertia are questions that have not yet received convincing answers because of the lack of direct observations. Hypothetical mechanisms have been proposed but not proven, such as the shredding of the membrane because of the osmotic...

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Section: Malaria Egress From Erythrocytes 4121mentioning

confidence: 65%

Section: Malaria Egress From Erythrocytes 4121mentioning

confidence: 99%

A novel mechanism for egress of malarial parasites from red blood cells

Abkarian

Massiera

Berry

et al. 2011

Blood

123

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“…Different membranous structures have been described in the erythrocyte cytoplasm that are potentially capable of participating in these trafficking events. These include the Maurer's clefts, which are closely apposed to the erythrocyte cytoskeleton at the surface, and the TVM, which emanates out of parasitophorous vacuole membrane (PVM) (6,8,9,40,41). Furthermore, the "BFA-sensitive" delivery of many parasite proteins to the erythrocyte surface indicates that vesicular membrane traffic, akin to that in mammalian cells, must also be operative in the erythrocyte cytoplasm.…”

Section: Figmentioning

confidence: 99%

Host Chaperones Are Recruited in Membrane-bound Complexes byPlasmodium falciparum

Gowrishankar¹,

Singh²,

Tatu

2002

Journal of Biological Chemistry

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The ability of malarial parasite to deploy proteins at the surface of infected erythrocytes is well known. After their synthesis within the parasite, the cargo proteins are exported from the parasite and carried across the erythrocyte cytoplasm to be delivered at the erythrocyte surface. Our knowledge about the mechanisms involved in this complex trafficking path is limited. We have addressed the involvement of chaperones in traffic across erythrocyte cytoplasm. Our analyses of the chaperones available to the parasite indicated that none of the reported chaperones of the parasite origin are present in the erythrocyte cytoplasm. The chaperones of the host (Hsp70, Hsp90, Hop60), on the other hand, were readily detected in the erythrocyte cytosol. Hypotonic lysis and detergent solubilization experiments indicated that unlike their soluble nature in normal erythrocytes, host chaperones are recruited in membrane-bound, detergent-resistant complexes in infected cells. The association of host-Hsp70 with detergent-resistant complexes was ATP-dependent. Importantly, host chaperones could be detected in knob-enriched fractions and could be cross-linked to the knob subunit, PfHRP1, in a large complex at the surface of the infected erythrocytes. Our results implicate host chaperones in the assembly of parasite proteins such as knob subunits at the erythrocyte surface.The cytoadherence property of Plasmodium falciparum-infected erythrocytes is central to the pathogenesis of malaria. The remodeled plasma membrane of the infected erythrocyte is mainly responsible for its ability to adhere to the vascular endothelium (1, 2). As part of the remodeling process, the parasite synthesizes and traffics several proteins to the erythrocyte membrane. Among these, proteins such as erythrocyte membrane proteins 1 and 3 (PfEMP1 and PfEMP3) 1 and histidine-rich protein (PfHRP1) are assembled in complexes identified as knobs, which form the sites of attachment to the endothelium (3). Understanding the trafficking and assembly steps of protein complexes at the surface of infected erythrocytes is an important priority in efforts to counter malaria.Very little is known about the mechanisms and components involved in trafficking parasite-encoded proteins to the erythrocyte membrane. Both, BFA-sensitive as well as BFA-insensitive routes of transport have been described for the delivery of parasite proteins (4-7). Atypical membrane elements like tubovesicular membranes (TVM), Maurer's clefts, and intraerythrocytic inclusions in the erythrocyte cytoplasm have been implicated in trafficking between the parasite and the erythrocyte surface (8, 9). The involvement of molecular chaperones in the erythrocyte cytoplasm is often suggested in facilitating the transport and assembly of proteins destined for the plasma membranes (10 -12). Several candidate chaperones belonging to the heat shock protein family have been identified in the parasite (13-19); however, only limited information is available about their localizations and possible functions. Most imp...

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“…5D and E). Previous work showed that MC and its associated proteins, including PfSBP-1, remain with the RBC ghost after schizont rupture and merozoite release (8,22,30). RBC ghosts were therefore prepared from late-stage schizonts and analyzed by an IFA with both anti-STEVOR and anti-PfSBP-1 antibodies to investigate the colocalization of these two proteins.…”

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confidence: 99%

Small Variant STEVOR Antigen Is Uniquely Located within Maurer's Clefts in Plasmodium falciparum -Infected Red Blood Cells

Kaviratne¹,

Khan²,

Jarra³

et al. 2002

Eukaryot Cell

119

140

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Malaria parasite antigens encoded by multigene families are important factors in virulence and in disease pathology. In Plasmodium falciparum, the virulence factor PfEMP-1 is encoded by the var multigene family and is exposed at the infected erythrocyte surface. PfEMP-1 is clonally variant, allowing the parasite to evade host immunity. The recently identified P. falciparum stevor multigene family and its products also have the potential to be involved in similar important aspects of host-parasite interactions. Here, we show tightly regulated stage-specific transcription of stevor occurring over just a few hours of the asexual parasite life cycle. Only a subset of stevor genes are transcribed in parasite populations maintained in cultures and in single micromanipulated parasites. Antibodies against STEVOR recognize proteins of the expected size (ϳ37 kDa) and localize STEVOR in Maurer's clefts, unique membranous structures located in the cytoplasm of infected erythrocytes. The fact that the timing of stevor expression and the location of STEVOR are clearly distinct from those of other parasite variant antigens suggests that this gene family may have a novel role in P. falciparum biology.To facilitate intraerythrocytic growth and survival, the asexual stage of malaria parasites makes extensive modifications to the parasitized host red blood cell (pRBC) (1). These modifications include the presentation of immunogenic parasite proteins at the surface of the pRBC, exposing the parasite to the effects of host immunity (14,25). Several of these surface proteins, for example, PfEMP-1 in Plasmodium falciparum and SICA antigen in P. knowelsi, induce antibody responses in the infected host which correlate with protection (11, 12). These molecules, encoded by multigene families, have also been shown to be clonally variant, allowing the parasite to evade host immunity. PfEMP-1, encoded by the var multigene family, facilitates the binding of pRBCs to a variety of host receptors on the endothelium, leading to the obstruction of blood vessels and contributing to the pathology and disease severity seen with P. falciparum. PfEMP-1 is thus considered a major virulence factor in P. falciparum infections in humans.Research on malaria multigene families has so far focused on var and rif in P. falciparum and py235 in P. yoelii. However, the Malaria Genome Project has now revealed additional families, including stevor in P. falciparum. Although relatively little is known about stevor, the possibility that its expression product, STEVOR, is involved in virulence, pathology, immunity, and immune evasion warrants more detailed investigation. First reported as 7h8, stevor was initially identified as an expressed sequence detected by a monoclonal antibody (29). There are about 30 to 40 copies of stevor per haploid genome, clustered within 50 kb of the telomeres on all chromosomes (13). Like rif, stevor has short first and longer (ϳ1-kb) second exons. The protein (STEVOR) has a predicted size of 30 to 40 kDa (13) and structurally may be simil...

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Identification of peripheral membrane proteins associated with the tubo-vesicular network of Plasmodium falciparum infected erythrocytes

Cited by 24 publications

References 23 publications

A novel mechanism for egress of malarial parasites from red blood cells

A novel mechanism for egress of malarial parasites from red blood cells

Host Chaperones Are Recruited in Membrane-bound Complexes byPlasmodium falciparum

Small Variant STEVOR Antigen Is Uniquely Located within Maurer's Clefts in Plasmodium falciparum -Infected Red Blood Cells

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