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

Blood. 2014 Nov 27;124(23):3459-68. doi: 10.1182/blood-2014-06-583054. Epub 2014 Aug 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism
  • Antigens, Protozoan / metabolism*
  • Cells, Cultured
  • Erythrocyte Membrane / metabolism
  • Erythrocyte Membrane / parasitology
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Host-Parasite Interactions
  • Humans
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / metabolism*
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / pathogenicity
  • Protein Transport
  • Protozoan Proteins / metabolism*
  • Transport Vesicles / metabolism
  • Transport Vesicles / parasitology
  • Virulence Factors / metabolism*

Substances

  • Actins
  • Antigens, Protozoan
  • Protozoan Proteins
  • STEVOR antigen, Plasmodium falciparum
  • Virulence Factors
  • erythrocyte membrane protein 1, Plasmodium falciparum