Article

Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum–Infected Erythrocytes

Department of Infectious Diseases, Parasitology, Heidelberg University, 69120 Heidelberg, Germany.
Science (Impact Factor: 33.61). 12/2011; 334(6060):1283-1286. DOI: 10.1126/science.1213775

ABSTRACT

The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins
to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host-derived actin
cytoskeleton within the cytoplasm of wild-type red blood cells that connected the Maurer’s clefts with the host cell membrane
and to which transport vesicles were attached. The actin cytoskeleton and the Maurer’s clefts were aberrant in erythrocytes
containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin
polymerization in vitro and may account for the protective role in malaria.

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Available from: Friedrich Frischknecht, Jun 01, 2014
    • "This hypothesis of poor attachment is consistent with the low number and very abbreviated nature of filamentous extensions from the few MC that could be found in our images of the AlF4 − -treated parasitized erythrocytes. The remodeling evident in our images of unroofed P. falciparuminfected erythrocytes also agrees with the cryoelectrontomography findings of Cyrklaff et al. (2011), who described altered host actin filaments in parasitized erythrocytes and connections of the MC by cytochalasin D-sensitive actin tethers to the interior of the erythrocyte membrane, and with the image reconstructions of Hanssen et al. (2008b), which showed small vesicles in association with tethered MC and extensions to the erythrocyte membrane. The observed dimensions of 100–650 nm for MC in unroofed preparations are in good agreement with the reported range 200–500 nm for MC at the periphery of the P. falciparum-infected erythrocytes in those reconstructions (Hanssen et al., 2010). "

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    • "In P. falciparum trophozoite-stage iRBCs, actin is remodeled to allow controlled trafficking of cargo vesicles important for functioning of Maurer's clefts and knobs [104], and can be oxidized [35] [101] [102]. Blood group O-derived hemoglobin variants somehow interfere with this remodeling and the establishment of a parasite-directed actin cytoskeleton in the infected cells [105]. In a rat model of oxidative stress, after use of x-irradiation to induce reactive oxygen species, actin was extensively oxidized, with partial oxidation of methionines including met-82 sulfone, oxidation of two of four tryptophans , and oxidation of several cysteines [106]. "
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