Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion

The most lethal form of malaria in humans is caused by . 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...

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Veröffentlicht in:eLife 2017-02, Vol.6
Hauptverfasser: Sisquella, Xavier, Nebl, Thomas, Thompson, Jennifer K, Whitehead, Lachlan, Malpede, Brian M, Salinas, Nichole D, Rogers, Kelly, Tolia, Niraj H, Fleig, Andrea, O'Neill, Joseph, Tham, Wai-Hong, David Horgen, F, Cowman, Alan F
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Sprache:eng
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Zusammenfassung:The most lethal form of malaria in humans is caused by . 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 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 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.21083