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

被引:59
作者
Rug, Melanie [1 ]
Cyrklaff, Marek [2 ]
Mikkonen, Antti [3 ]
Lemgruber, Leandro [2 ]
Kuelzer, Simone [3 ]
Sanchez, Cecilia P. [2 ]
Thompson, Jennifer [1 ]
Hanssen, Eric [4 ]
O'Neill, Matthew [1 ]
Langer, Christine [1 ]
Lanzer, Michael [2 ]
Frischknecht, Friedrich [2 ]
Maier, Alexander G. [3 ]
Cowman, Alan F. [1 ,5 ]
机构
[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia
[2] Heidelberg Univ, Dept Infect Dis Parasitol, Heidelberg, Germany
[3] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia
[4] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3052, Australia
[5] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;
关键词
RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; MAURERS CLEFTS; PARASITOPHOROUS VACUOLE; TARGETED MUTAGENESIS; PARASITE PROTEINS; PLASMEPSIN V; TRAFFICKING; SURFACE; MEMBRANE;
D O I
10.1182/blood-2014-06-583054
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:3459 / 3468
页数:10
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