PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes
Benjamin Liffner, Sonja Frolich, Gary K Heinemann, Boyin Liu, Stuart A Ralph, Matthew WA Dixon, Tim-Wolf Gilberger, Danny W Wilson
Nature Communications | NATURE PUBLISHING GROUP | Published : 2020
The disease-causing blood-stage of the Plasmodium falciparum lifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the merozoite. Here we identify an essential role for the conserved protein P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 1 (PfCERLI1) in rhoptry function. We show that PfCERLI1 localises to the cytosolic face of the rhoptry bulb membrane and knockdown of PfCERLI1 inhibits merozoite invasion. While schizogony and merozoite organelle biogenesis appear normal, biochemical techniq..View full abstract
Awarded by NHMRC
We thank the Australian Red Cross Blood Bank for the provision of human blood. We thank Prof. Alan Cowman for provision of CyRPA, RON4, EBA175 and GAP45 antibodies, Dr. Paul Gilson for EXP2 antibodies, A/Prof. Wai-Hong Tham for RH4 antibodies, and Prof. Leann Tilley for ERC and GAPDH antibodies. We also thank Dr. Paul Gilson for the PTEX150HAGlmS transfection vector. Confocal microscopy was performed at Adelaide Microscopy, University of Adelaide, and super-resolution microscopy was performed at the Centre for Cancer Biology Cytometry Facility, The University of South Australia. We especially thank Dr. Jane Sibbons from Adelaide Microscopy for assistance with confocal microscopy. Electron microscopy was performed at the Bio21 Institute Advanced Microscopy Facility, The University of Melbourne (www.microscopy.unimelb.edu.au).For provision of the SLI-TGD vector, we thank Dr. Tobias Spielmann. We thank Dr. Brad Sleebs for Compound 1. We thank Arne Alder and Sarah Lemcke for help with SLI-TGD transfection and parasite culture. This work was supported by funding from the NHMRC (Project Grant APP1143974, D.W.W.), University of Adelaide Beacon Fellowship (D.W.W.), DAAD/Universities Australia joint research co-operation scheme (T. G., D.W.W., B.L.), Australian Government Research Training Program Scholarship (B. L.), South Australian Commonwealth Scholarship (B.L.).