Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes
Jennifer C Volz, Alan Yap, Xavier Sisquella, Jenn K Thompson, Nicholas TY Lim, Lachlan W Whitehead, Lin Chen, Marko Lampe, Wai-Hong Tham, Danny Wilson, Thomas Nebl, Danushka Marapana, Tony Triglia, Wilson Wong, Kelly L Rogers, Alan F Cowman
CELL HOST & MICROBE | CELL PRESS | Published : 2016
Plasmodium falciparum parasites in the merozoite stage invade human erythrocytes and cause malaria. Invasion requires multiple interactions between merozoite ligands and erythrocyte receptors. P. falciparum reticulocyte binding homolog 5 (PfRh5) forms a complex with the PfRh5-interacting protein (PfRipr) and Cysteine-rich protective antigen (CyRPA) and binds erythrocytes via the host receptor basigin. However, the specific role that PfRipr and CyRPA play during invasion is unclear. Using P. falciparum lines conditionally expressing PfRipr and CyRPA, we show that loss of PfRipr or CyRPA function blocks growth due to the inability of merozoites to invade erythrocytes. Super-resolution microsco..View full abstract
Awarded by National Health and Medical Research Council of Australia (NHMRC)
We thank the Australian Red Cross Blood Service for blood and the Walter and Eliza Hall Institute Monoclonal Laboratory for monoclonal antibodies; Jose-Juan Lopez-Rubio for CRISPR/Cas9 plasmids; Paul Gilson for advice; Eugene Kapp for MSPnr protein database; and Advanced Light Microscopy Facility (ALMF), European Molecular Biology Laboratory (EMBL-Heidelberg), and Leica for support. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) (grant 637406 to A.F.C. and 1026581 to W.-H.T.) and by a Victorian State Government Operational Infrastructure Support grant. A.Y. and D.W. received a Paddy Pearl Fellowship and a NHMRC Peter Doherty Australian Biomedical Fellowship, respectively. W.-H.T. is supported by an ARC Future Fellowship. A.F.C. is a Howard Hughes Medical Institute International Scholar.