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.
Article and author information
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.
Reviewing Editor
- Stephen C. Harrison, Harvard Medical School, United States
Version history
- Received: August 30, 2016
- Accepted: February 9, 2017
- Accepted Manuscript published: February 22, 2017 (version 1)
- Version of Record published: March 2, 2017 (version 2)
- Version of Record updated: March 3, 2017 (version 3)
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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