A Maurer's cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells

Cooke, B. M., Buckingham, D. W., Glenister, F. K., Fernandez, K. M., Bannister, L. H., Marti, M. , Mohandas, N. and Coppel, R. L. (2006) A Maurer's cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells. Journal of Cell Biology, 172(6), pp. 899-908. (doi:10.1083/jcb.200509122) (PMID:16520384) (PMCID:PMC2063733)

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Abstract

The high mortality of Plasmodium falciparum malaria is the result of a parasite ligand, PfEMP1 (P. falciparum) erythrocyte membrane protein 1), on the surface of infected red blood cells (IRBCs), which adheres to the vascular endothelium and causes the sequestration of IRBCs in the microvasculature. PfEMP1 transport to the IRBC surface involves Maurer's clefts, which are parasite-derived membranous structures in the IRBC cytoplasm. Targeted gene disruption of a Maurer's cleft protein, SBP1 (skeleton-binding protein 1), prevented IRBC adhesion because of the loss of PfEMP1 expression on the IRBC surface. PfEMP1 was still present in Maurer's clefts, and the transport and localization of several other Maurer's cleft proteins were unchanged. Maurer's clefts were altered in appearance and were no longer found as close to the periphery of the IRBC. Complementation of mutant parasites with sbp1 led to the reappearance of PfEMP1 on the IRBC surface and the restoration of adhesion. Our results demonstrate that SBP1 is essential for the translocation of PfEMP1 onto the surface of IRBCs and is likely to play a pivotal role in the pathogenesis of P. falciparum malaria.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias
Authors: Cooke, B. M., Buckingham, D. W., Glenister, F. K., Fernandez, K. M., Bannister, L. H., Marti, M., Mohandas, N., and Coppel, R. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Cell Biology
Publisher:Rockefeller University Press
ISSN:0021-9525
ISSN (Online):1540-8140
Published Online:06 March 2006
Copyright Holders:Copyright © 2006 The Authors
First Published:First published in Journal of Cell Biology 172(6):899-908
Publisher Policy:Reproduced under a Creative Commons License

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