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Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton.

Rug M, Cyrklaff M, Mikkonen A, Lemgruber L, Kuelzer S, Sanchez CP, Thompson J, Hanssen E, O'Neill M, Langer C, Lanzer M, Frischknecht F, Maier AG, Cowman AF

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  • Journal Blood

  • Published 19 Aug 2014

  • Volume 124

  • ISSUE 23

  • Pagination 3459-68

  • DOI 10.1182/blood-2014-06-583054

Abstract

Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell mediated by trafficking of several hundred effector proteins to the RBC compartment. The exported virulence protein, P falciparum erythrocyte membrane protein 1 (PfEMP1), is responsible for cytoadherence of infected cells to host endothelial receptors. Maurer clefts are organelles essential for protein trafficking, sorting, and assembly of protein complexes. Here we demonstrate that disruption of PfEMP1 trafficking protein 1 (PfPTP1) function leads to severe alterations in the architecture of Maurer's clefts. Furthermore, 2 major surface antigen families, PfEMP1 and STEVOR, are no longer displayed on the host cell surface leading to ablation of cytoadherence to host receptors. PfPTP1 functions in a large complex of proteins and is required for linking of Maurer's clefts to the host actin cytoskeleton.