<i>Plasmodium falciparum</i>apical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development

Bannister, L. H.; Hopkins, J. M.; Dluzewski, Anton R.; Margos, Gabriele; Williams, Ian T.; Blackman, Michael J.; Kocken, Clemens H. M.; Thomas, Alan W.; Mitchell, G. H.

doi:10.1242/jcs.00665

Cited by 143 publications

(118 citation statements)

References 52 publications

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“…As shown by electron microscopy, the mitochondrion and the apicoplast are aligned asymmetrically in the P. falciparum merozoites along the same side as the microtubules (16,17). We found that, in addition to HA-PfROM1, other organelles in P. falciparum merozoites are also aligned on the same side of the parasite nucleus as the microtubules (Fig.…”

Section: Ha-pfrom1 Is In Close Proximity To the Merozoite Subpellicularsupporting

confidence: 59%

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Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease

Singh

Plassmeyer

Gaur

et al. 2007

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

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Compartmentalization of proteins into subcellular organelles in eukaryotic cells is a fundamental mechanism of regulating complex cellular functions. Many proteins of Plasmodium falciparum merozoites involved in invasion are compartmentalized into apical organelles. We have identified a new merozoite organelle that contains P. falciparum rhomboid-1 (PfROM1), a protease that cleaves the transmembrane regions of proteins involved in invasion. By immunoconfocal microscopy, PfROM1 was localized to a single, thread-like structure on one side of the merozoites that appears to be in close proximity to the subpellicular microtubules. PfROM1 was not found associated with micronemes, rhoptries, or dense granules, the three identified secretory organelles of invasion. Release of merozoites from schizonts resulted in the movement of PfROM1 from the lateral asymmetric localization to the merozoite apical pole and the posterior pole. We have named this single thread-like organelle in merozoites, the mononeme. malaria A picomplexa are named for a set of secretory organelles (rhoptries, micronemes, and dense granules) found at the apical end of these parasites, the end that invades cells in the vertebrate host (1). These organelles were first identified by their distinct morphological appearances in transmission electron microscopy (2-4). Many parasite proteins required for invasion of erythrocytes are segregated into the micronemes (5, 6). For example, Plasmodium falciparum apical membrane antigen 1 (AMA1) is held in the micronemes in merozoites inside of erythrocytes. Release from the erythrocyte triggers the movement of AMA1 to the cell surface where it functions in invasion (7,8). Similarly, rhoptries sequester a different set of proteins and their contents are released onto the erythrocyte surface (4, 9), presumably to break the local cytoskeleton and to initiate formation of the parasitophorous vacuole. Taken together, these observations provide evidence for compartmentalization of parasite proteins into distinct organelles with related functions in invasion. Presumably, such compartmentalization provides a mechanism for orchestrating the timing of delivery or activity of the proteins during the complex process of invasion.Apicomplexan rhomboid proteases have been implicated to play an important role in host cell invasion (10, 11). PfROM1 substrates have been identified in P. falciparum by using a mammalian cell-based proteolytic assay (12) that identified various micronemal proteins as potential substrates including AMA1. Because AMA1 has been implicated as essential for invasion, separation of PfROM1 from this substrate within the parasite may be important to prevent premature cleavage. Studies defining the spatiotemporal distribution of PfROM1 in P. falciparum merozoites are, therefore, likely to contribute to a clearer understanding of its role in erythrocyte invasion. Expression of hemagglutinin (HA)-tagged P. falciparum rhomboid-1 (PfROM1) localizes it to a new subcellular compartment distinct from other known meroz...

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Section: Ha-pfrom1 Is In Close Proximity To the Merozoite Subpellicularsupporting

confidence: 59%

“…7, 8, and 10). We have shown that the location of the full-length PfROM1 is separate from AMA1 and EBA175, two proteins found in micronemes (17,23). The PfROM1 construct used here was similar to that used for localization of T. gondii ROM1 (10).…”

Section: Discussionmentioning

confidence: 93%

Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease

Singh

Plassmeyer

Gaur

et al. 2007

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

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“…55 Micronemes are round, proteindense, membrane-bound organelles that have been shown to contain proteins secreted through their ducts near the apical end. 56,57 The ookinete pellicle includes the parasite plasma membrane, the inner membrane complex, and subpellicular microtubules. 35 The method presented here consistently produced large quantities of sexual stage forms of the human malaria parasite P. falciparum .…”

Section: Ultrastructural Analysis Of P Falciparum Sexual Stage Parasmentioning

confidence: 99%

In Vitro Generation of Plasmodium falciparum Ookinetes

Bounkeua¹,

Li²,

Vinetz³

2010

The American Society of Tropical Medicine and Hygiene

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Plasmodium transmission from the human host to the mosquito depends on the ability of gametocytes to differentiate into ookinetes, the invasive form of the parasite that invades and establishes infection in the mosquito midgut. The biology of P. falciparum ookinetes is poorly understood, because sufficient quantities of this stage of this parasite species have not been obtained for detailed study. This report details methods to optimize production of P. falciparum sexual stage parasites, including ookinetes. Flow cytometric sorting was used to separate diploid/tetraploid zygotes and ookinetes from haploid gametetocytes and unfertilized gametes based on DNA content. Consistent production of 106–107 P. falciparum ookinetes per 10 mL culture was observed, with ookinete transformation present in 10–40% of all parasite forms. Transmission electron micrographs of cultured parasites confirmed ookinete development.

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“…This result indicates that molecules other than the parasite Duffy binding protein family are exposed by enzyme treatment to form the junction between Duffy negative human erythrocytes and P. knowlesi merozoites. One of the possible junction-forming molecules is apical merozoite antigen 1 (AMA1), which is found in the micronemes (4). Half of the cytoplasmic domain of AMA1 is highly conserved in all Plasmodium species, suggesting a role for signaling or interaction with the actin-myosin motor once the extracellular domain is engaged.…”

Section: T He Complex Multistep Process Of Invasion Of Erythrocytes Bymentioning

confidence: 99%

Domain III of Plasmodium falciparum apical membrane antigen 1 binds to the erythrocyte membrane protein Kx

Kato

Mayer

Singh

et al. 2005

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

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Plasmodium falciparum apical membrane antigen 1 (AMA1) is located in the merozoite micronemes, an organelle that contains receptors for invasion, suggesting that AMA1 may play a role in this process. However, direct evidence that P. falciparum AMA1 binds to human erythrocytes is lacking. In this study, we determined that domain III of AMA1 binds to the erythrocyte membrane protein, Kx, and that the rate of invasion of Kx null erythrocytes is reduced, indicating a significant but not unique role of AMA1 and Kx in parasite invasion of erythrocytes. Domains I͞II͞III, domains I͞II and domain III of AMA1 were expressed on the surface of CHO-K1 cells, and their ability to bind erythrocytes was determined. We observed that each of these domains failed to bind untreated human erythrocytes. In contrast, domain III, but not the other domains of AMA1, bound to trypsin-treated human erythrocytes. We tested the binding of AMA1 to trypsin-treated genetically mutant human erythrocytes, missing various erythrocyte membrane proteins. AMA1 failed to bind trypsin-treated Kx null (McLeod) erythrocytes, which lack the Kx protein. Furthermore, treatmentofhumanerythrocyteswithtrypsin,followedby␣-chymotrypsin, cleaved Kx and destroyed the binding of AMA1 to human erythrocytes. Lastly, the rate of invasion of Kx null erythrocytes by P. falciparum was significantly lower than Kx-expressing erythrocytes. Taken together, our data suggest that AMA1 plays an important, but not exclusive, role in invasion of human erythrocytes through a process that involves exposure or modification of the erythrocyte surface protein, Kx, by a trypsin-like enzyme. T he complex multistep process of invasion of erythrocytes byPlasmodium falciparum begins with the binding of any surface of the merozoite, followed by reorientation to put the merozoite's apical end in close apposition to the erythrocyte surface. The apical end of merozoites contains the organelles of invasion, including the micronemes that contain receptors such as members of the Duffy binding protein family of erythrocytebinding ligands (1). A junction forms between P. knowlesi merozoites and the erythrocyte before the merozoite is brought into the erythrocyte. The junction only forms and invasion only occurs between P. knowlesi merozoites and Duffy blood group positive human erythrocytes. Duffy null cells fail to form a junction and are not invaded by P. knowlesi merozoites (2). However, trypsin-or neuraminidase-treated human Duffy null erythrocytes could form a junction and were invaded by P. knowlesi merozoites (3) despite the fact that untreated and trypsin-treated human Duffy null cells fail to bind any of the P. knowlesi Duffy binding proteins expressed on COS-7 cells (2). This result indicates that molecules other than the parasite Duffy binding protein family are exposed by enzyme treatment to form the junction between Duffy negative human erythrocytes and P. knowlesi merozoites. One of the possible junction-forming molecules is apical merozoite antigen 1 (AMA1), which is found in the mic...

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Plasmodium falciparumapical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development

Cited by 143 publications

References 52 publications

Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease

Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease

In Vitro Generation of Plasmodium falciparum Ookinetes

Domain III of Plasmodium falciparum apical membrane antigen 1 binds to the erythrocyte membrane protein Kx

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