Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion
Journal Title
Elife
Publication Type
Journal Article
Abstract
The most lethal form of malaria in humans is caused by Plasmodium falciparum. These parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. The parasite makes initial contact with the erythrocyte followed by dramatic deformations linked to the function of the Erythrocyte binding antigen family and P. falciparum reticulocyte binding-like families. We show EBA-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin A and activating a phosphorylation cascade that includes erythrocyte cytoskeletal proteins resulting in changes in the viscoelastic properties of the host cell. TRPM7 kinase inhibitors FTY720 and waixenicin A block the changes in the deformability of erythrocytes and inhibit merozoite invasion by directly inhibiting the phosphorylation cascade. Therefore, binding of P. falciparum parasites to the erythrocyte directly activate a signaling pathway through a phosphorylation cascade and this alters the viscoelastic properties of the host membrane conditioning it for successful invasion.
Publisher
eLIFE
WEHI Research Division(s)
Infection And Immunity; Systems Biology And Personalised Medicine
PubMed ID
28226242
Open Access at Publisher's Site
https://elifesciences.org/content/6/e21083
NHMRC Grants
NHMRC/637406 NHMRC/1026581
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-04-06 09:27:23
Last Modified: 2017-04-06 12:38:03
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