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

Melanie Rug; Marek Cyrklaff; Antti Mikkonen; Leandro Lemgruber; Simone Kuelzer; Cecilia P. Sanchez; Jennifer Thompson; Eric Hanssen; Matthew O'Neill; Christine Langer; Michael Lanzer; Friedrich Frischknecht; Alexander G. Maier; Alan F. Cowman

doi:10.1182/blood-2014-06-583054

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

Melanie Rug^*, Marek Cyrklaff, Antti Mikkonen, Leandro Lemgruber, Simone Kuelzer, Cecilia P. Sanchez, Jennifer Thompson, Eric Hanssen, Matthew O'Neill, Christine Langer, Michael Lanzer, Friedrich Frischknecht, Alexander G. Maier, Alan F. Cowman

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3459-3468
Number of pages	10
Journal	Blood
Volume	124
Issue number	23
DOIs	https://doi.org/10.1182/blood-2014-06-583054
Publication status	Published - 19 Aug 2014

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Rug, M., Cyrklaff, M., Mikkonen, A., Lemgruber, L., Kuelzer, S., Sanchez, C. P., Thompson, J., Hanssen, E., O'Neill, M., Langer, C., Lanzer, M., Frischknecht, F., Maier, A. G., & Cowman, A. F. (2014). Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton. Blood, 124(23), 3459-3468. https://doi.org/10.1182/blood-2014-06-583054

@article{1bb4f81bf1294f92819b112f95d01b71,

title = "Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton",

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.",

author = "Melanie Rug and Marek Cyrklaff and Antti Mikkonen and Leandro Lemgruber and Simone Kuelzer and Sanchez, {Cecilia P.} and Jennifer Thompson and Eric Hanssen and Matthew O'Neill and Christine Langer and Michael Lanzer and Friedrich Frischknecht and Maier, {Alexander G.} and Cowman, {Alan F.}",

note = "Publisher Copyright: {\textcopyright} 2014 by The American Society of Hematology.",

year = "2014",

month = aug,

day = "19",

doi = "10.1182/blood-2014-06-583054",

language = "English",

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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 2014, 'Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton', Blood, vol. 124, no. 23, pp. 3459-3468. https://doi.org/10.1182/blood-2014-06-583054

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T1 - Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

AU - Rug, Melanie

AU - Cyrklaff, Marek

AU - Mikkonen, Antti

AU - Lemgruber, Leandro

AU - Kuelzer, Simone

AU - Sanchez, Cecilia P.

AU - Thompson, Jennifer

AU - Hanssen, Eric

AU - O'Neill, Matthew

AU - Langer, Christine

AU - Lanzer, Michael

AU - Frischknecht, Friedrich

AU - Maier, Alexander G.

AU - Cowman, Alan F.

PY - 2014/8/19

Y1 - 2014/8/19

N2 - 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.

AB - 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.

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DO - 10.1182/blood-2014-06-583054

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VL - 124

SP - 3459

EP - 3468

JO - Blood

JF - Blood

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ER -

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

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