title: Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum.
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.
authors.affiliation: Division of Molecular Genetics & Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Gao
authors.forename: Karthigayan
authors.initials: K
authors.lastname: Gunalan
authors.forename: Sally Shu Lin
authors.initials: SS
authors.lastname: Yap
authors.forename: Peter R
authors.initials: PR
authors.lastname: Preiser
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology; D052940:Merozoites / Q000254:growth & development / Q000502:physiology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D002118:Calcium