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- Title
Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion.
- Authors
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; Wai-Hong Tham; Horgen, F. David; Cowman, Alan F.
- 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.
- Subjects
MALARIA; PLASMODIUM falciparum; ERYTHROCYTES; LIGANDS (Biochemistry); RETICULOCYTES
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.21083