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During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol (1-6). These proteins have a variety of roles that are essential to virulence or parasite growth (7). There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins (8,9). One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX) (10). Although PTEX has been linked to the export of one class of exported proteins (10,11), there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D) (1,2) and PEXEL-negative exported proteins (PNEPs) (6). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite's capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target., To address the role of PTEX in protein export directly, we examined parasite lines defective in PTEX components for their capacity to translocate exported proteins. Two PTEX components, TRX2 and [...]

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease., Malaria is a disease of global importance causing significant morbidity and death (1). Plasmodium falciparum is responsible for the lethal form of malaria and morphological changes occur in infected erythrocytes [...]

Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention. Malaria parasite virulence During intracellular infection of erythrocytes, malaria parasites reside in vacuoles from where they export many proteins into the host cell. These protein secretions play an important role in the virulence and viability of the Plasmodium parasite. The protein export machinery involved in this process has now been identified. Termed PTEX (for Plasmodium Translocon of EXported proteins), it is an ATP-powered complex located in the vacuole membrane, and may provide a new target for antimalarial drugs. Malaria parasites reside in vacuoles during intracellular infection of erythrocytes and export many proteins into the host cell, a process that is essential for the virulence and viability of Plasmodium. Whereas transport across the parasite membrane is known to rely on the secretory pathway, the transporter responsible for the translocation of proteins across the vacuole membrane is now identified., Author(s): Tania F. de Koning-Ward [sup.1] [sup.2] , Paul R. Gilson [sup.1] [sup.3] , Justin A. Boddey [sup.1] , Melanie Rug [sup.1] , Brian J. Smith [sup.1] , Anthony T. [...]

In some types of unicellular algae, the chloroplasts have their own nucleus -- a legacy of the time when the chloroplast was a free-living cell. The sequence of the genome in one such nucleus is now revealed., Author(s): Paul R. Gilson [sup.1] , Geoffrey I. McFadden [sup.1] Author Affiliations: (1) Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Victoria, Australia The [...]