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Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum

Author

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  • Xiaohong Gao

    (School of Biological Sciences, Nanyang Technological University)

  • Karthigayan Gunalan

    (School of Biological Sciences, Nanyang Technological University)

  • Sally Shu Lin Yap

    (School of Biological Sciences, Nanyang Technological University)

  • Peter R. Preiser

    (School of Biological Sciences, Nanyang Technological University)

Abstract

Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH–host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention.

Suggested Citation

  • Xiaohong Gao & Karthigayan Gunalan & Sally Shu Lin Yap & Peter R. Preiser, 2013. "Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3862
    DOI: 10.1038/ncomms3862
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    Cited by:

    1. Melissa N. Hart & Franziska Mohring & Sophia M. DonVito & James A. Thomas & Nicole Muller-Sienerth & Gavin J. Wright & Ellen Knuepfer & Helen R. Saibil & Robert W. Moon, 2023. "Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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