Journal article

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

Xavier Sisquella, Thomas Nebr, Jennifer K Thompson, Lachlan Whitehead, Brian M Malpede, Nichole D Salinas, Kelly Rogers, Niraj H Tolia, Andrea Fleig, Joseph O'Neill, Wai-Hong Timm, F David Horgen, Alan F Cowman

eLife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2017

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 waixe..

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Grants

Awarded by Howard Hughes Medical Institue


Awarded by National Health and Medical Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

Howard Hughes Medical Institue HHMI International Scholar Award 55007645 Alan F CowmanNational Health and Medical Research Council NHMRC Program Grant 637406 Alan F CowmanAustralian Research Council Australian Research Council Future Fellowship Wai-Hong ThamNational 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 CowmanNational Health and Medical Research Council 1026581 Alan F CowmanThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.