Erythrocytic casein kinase II regulates cytoadherence of Plasmodium falciparum-infected red blood cells.

The Journal of Biological Chemistry
Rachna HoraAmit Sharma

Abstract

Plasmodium falciparum malaria is a major human health scourge and a key cause of mortality. Its pathogenicity partly results from the phenomenon of "cytoadherence" mediated by the PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) family. Extracellular domains of PfEMP1s are variable and bind various host endothelial receptors, whereas their cytoplasmic domains (VARCs) are relatively conserved. VARCs affix PfEMP1s in the human erythrocyte membrane by interacting with host cytoskeleton proteins and exported parasite proteins. Here, we provide in vitro and in vivo evidence for PfEMP1 phosphorylation (on VARC) and propose an important function for this modification. Specific inhibitors and enhancers have been used to identify erythrocytic casein kinase II (CKII) as the enzyme responsible for VARC modification activity. We have also delineated probable CKII target residues on VARC, which mainly reside in an N-terminal acidic cluster. Our data show that VARC phosphorylation alters its binding to parasite encoded knob-associated histidine-rich protein (KAHRP). Finally, we demonstrate reduced cytoadherence of infected RBCs to endothelial receptors like ICAM-1 and CSA (these contribute to cerebral and placental malaria, resp...Continue Reading

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Citations

Sep 24, 2010·PLoS Computational Biology·Thomas S RaskThomas Lavstsen
Jun 18, 2014·Journal of Structural and Functional Genomics·Sameena KhanAmit Sharma
Jul 23, 2014·Journal of Structural and Functional Genomics·Vitul JainManickam Yogavel
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Nov 14, 2014·The Biochemical Journal·Arvind Sharma, Amit Sharma
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Methods Mentioned

BETA
gel filtration
electrophoresis
in-gel kinase assay
enzyme-linked immunosorbent assay
immunoprecipitation

Software Mentioned

DisoPred
ImageJ
ClustalW

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