Identification of a role for the PfEMP1 semi-conserved head structure in protein trafficking to the surface of Plasmodium falciparum infected red blood cells - Institut Pasteur Access content directly
Journal Articles Cellular Microbiology Year : 2010

Identification of a role for the PfEMP1 semi-conserved head structure in protein trafficking to the surface of Plasmodium falciparum infected red blood cells

Abstract

Transport of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) variants to the red blood cell (RBC) surface enables malarial parasite evasion of host immunity by modifying the antigenic and adhesive properties of infected RBCs. In this study, we applied the Bxb1 integrase system to integrate transgenes encoding truncated PfEMP1-GFP fusions into cytoadherent A4 parasites and characterize their surface transport requirements. Our studies revealed that the semiconserved head structure of PfEMP1 proteins, in combination with the predicted transmembrane region and cytoplasmic tail, encodes sufficient information for RBC surface display. In contrast, miniPfEMP1 proteins with truncated head structures were exported to the RBC cytoplasm but were not detected at the RBC surface by flow cytometry or immuno-electron microscopy. We demonstrated the absence of a mechanistic barrier to having native and miniPfEMP1 proteins displayed simultaneously at the RBC surface. However, surface exposed miniPfEMP1 proteins did not convey cytoadherence properties to their host cells, implicating potential steric considerations in host-receptor interactions or the need for multiple domains to mediate cell binding. This study establishes a new system to investigate PfEMP1 transport and demonstrates that the PfEMP1 semi-conserved head structure is under selection for protein transport, in addition to its known roles in adhesion.
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pasteur-03506821 , version 1 (02-01-2022)

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Martin Melcher, Rebecca A. Muhle, Philipp P. Henrich, Susan M. Kraemer, Marion Avril, et al.. Identification of a role for the PfEMP1 semi-conserved head structure in protein trafficking to the surface of Plasmodium falciparum infected red blood cells. Cellular Microbiology, 2010, 12 (10), pp.1446 - 1462. ⟨10.1111/j.1462-5822.2010.01481.x⟩. ⟨pasteur-03506821⟩

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