P. falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion
- The Walter and Eliza Hall Institute of Medical Research, Australia
- Washington University School of Medicine, United States
- Hawaii Pacific University, United States
- University of Hawaii, United States
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 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 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.
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Author details
Funding
Howard Hughes Medical Institute (HHMI International Scholar Award 55007645)
- Alan F Cowman
National Health and Medical Research Council (NHMRc Program Grant 637406)
- Alan F Cowman
Australian Research Council (Australian Research Council Future Fellowship)
- Wai-Hong Tham
National Health and Medical Research Council (IRIISS grant)
- Xavier Sisquella
- Thomas Nebl
- Jennifer K Thompson
- Lachlan Whitehead
- Kelly Rogers
- Joseph O'Neill
- Wai-Hong Tham
- Alan F Cowman
National Health and Medical Research Council (1026581)
- Alan F Cowman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Sisquella et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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P. falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion
eLife 6:e21083.
https://doi.org/10.7554/eLife.21083
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