Title
Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites
Date Issued
01 June 2019
Access level
open access
Resource Type
journal article
Author(s)
Knuepfer E.
Wright K.E.
Prajapati S.K.
Rawlinson T.A.
Mohring F.
Koch M.
Lyth O.R.
Howell S.A.
Snijders A.P.
Moon R.W.
Draper S.J.
Rosanas-Urgell A.
Higgins M.K.
Baum J.
Holder A.A.
Universidad Peruana Cayetano Heredia
Abstract
Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediated by the interaction between PfRH5 and erythrocyte receptor basigin (BSG). However, whilst CyRPA and RIPR are present in most Plasmodium species, RH5 is found only in the small Laverania subgenus. Existence of a complex analogous to PfRH5-PfCyRPA-PfRIPR targeting BSG, and involvement of CyRPA and RIPR in invasion, however, has not been addressed in non-Laverania parasites. Here, we establish that unlike P. falciparum, P. knowlesi and P. vivax do not universally require BSG as a host cell invasion receptor. Although we show that both PkCyRPA and PkRIPR are essential for successful invasion of erythrocytes by P. knowlesi parasites in vitro, neither protein forms a complex with each other or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex whereas PkCyRPA appears to function without other parasite binding partners. It therefore appears that in the absence of RH5, outside of the Laverania subgenus, RIPR and CyRPA have different, independent functions crucial for parasite survival.
Volume
15
Issue
6
Scopus EID
2-s2.0-85068588097
PubMed ID
Source
PLoS Pathogens
Resource of which it is part
PLoS Pathogens
ISSN of the container
15537366
Source funding
Center for Outcomes Research and Evaluation, Yale School of Medicine
Sponsor(s)
This work was funded by the Francis Crick Institute (www.crick.ac.uk), the Wellcome Trust (www.wellcome.ac.uk), the UK Medical Research Council (MRC; www.mrc.ac.uk) and the Flemish government. E.K. and A.A.H. are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (www. cancerresearchuk.org) (FC001097), the UK MRC (FC001097) and the Wellcome Trust (FC001097). K. E. W. holds a Sir Henry Wellcome Fellowship (107366/Z/15/Z) and J. B. and M.K.H. hold Investigator Awards (100993/Z/13/Z and 101020/ Z/13/Z) from the Wellcome Trust. T. A. R. holds a Wellcome Trust Research Training Fellowship (108734/Z/15/Z). S. J. D. is a Jenner Investigator, a Lister Institute (www.lister-institute.org.uk) Research Prize Fellow and a Wellcome Trust Senior Fellow (106917/Z/15/Z). R.W.M. and F.M. are supported by an MRC Career Development Award (MR/M021157/1) jointly funded by the UK MRC and UK Department for International Development and A.R.U. is supported financially by the Flemish Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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