Journal article
Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites
B Liffner, JM Balbin, GJ Shami, G Siddiqui, J Strauss, S Frölich, GK Heinemann, EM Edwards, A Alder, JS Wichers, DJ Creek, L Tilley, MWA Dixon, TW Gilberger, DW Wilson
Communications Biology | NATURE PORTFOLIO | Published : 2022
Open access
Abstract
Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led ..
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Awarded by Jürgen Manchot Stiftung
Funding Acknowledgements
We thank Prof. Alan Cowman for provision of RON4, EBA175 and GAP45 antibodies, A/Prof. Wai-Hong Tham for RH4 antibodies, Dr. Matt Dixon for GAPDH and ERC antibodies. We also thank Dr. Paul Gilson for the PTEX150HAGlmS transfection vector, MSP1-19 and EXP2 antibodies. Fluorescence imaging was performed at Adelaide Microscopy (The University of Adelaide) and the Centre for Cancer Biology (UniSA). Electron microscopy was performed at the Ian Holmes Imaging Centre, Bio21, 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 the Australian Red Cross Blood Bank for the provision of human blood that was collected with informed consent of the donors. We thank the VEuPathDB team, as access to their database enabled much of this research. This work was supported by funding from the NHMRC (Project Grant APP1143974, D.W.W.), University of Adelaide Beacon Fellowship and Hospital Research Foundation Fellowship (D.W.W.), DAAD/Universities Australia joint research co-operation scheme (T.G., D.W.W., B.L., J.B.), Australian Government Research Training Program Scholarship (B.L., J.B.), South Australian Commonwealth Scholarship (B.L.), DFG BA5213/31 (J.S.W.) and Jurgen Manchot-Stiftung fellowship (A.A.).