Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion
- Author(s)
- Sisquella, X; Nebl, T; Thompson, JK; Whitehead, L; Malpede, BM; Salinas, ND; Rogers, K; Tolia, NH; Fleig, A; O'Neill, J; Tham, WH; David Horgen, F; Cowman, AF;
- 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
- Research Division(s)
- Infection And Immunity; Systems Biology And Personalised Medicine
- PubMed ID
- 28226242
- Publisher's Version
- https://doi.org/10.7554/eLife.21083
- Open Access at Publisher's Site
https://elifesciences.org/content/6/e21083- NHMRC Grants
- NHMRC/637406, NHMRC/1026581,
- Terms of Use/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