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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism
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Actin Cytoskeleton / ultrastructure*
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Actins / metabolism*
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Cytoplasm / ultrastructure
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Electron Microscope Tomography
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Erythrocyte Membrane / ultrastructure
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Erythrocytes / metabolism
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Erythrocytes / parasitology*
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Erythrocytes / ultrastructure*
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Hemoglobin A / analysis
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Hemoglobin C / analysis*
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Hemoglobin C / genetics
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Hemoglobin C Disease / complications
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Hemoglobin C Disease / metabolism
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Hemoglobin, Sickle / analysis*
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Hemoglobin, Sickle / genetics
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Humans
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Malaria, Falciparum / complications
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Malaria, Falciparum / metabolism
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Malaria, Falciparum / pathology
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Oxidation-Reduction
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Plasmodium falciparum / growth & development
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Plasmodium falciparum / physiology*
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Protein Transport
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Protozoan Proteins / metabolism
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Sickle Cell Trait / complications
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Sickle Cell Trait / metabolism
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Transport Vesicles / ultrastructure
Substances
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Actins
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Hemoglobin, Sickle
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Protozoan Proteins
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Hemoglobin C
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Hemoglobin A