Differences in erythrocyte receptor specificity of different parts of the Plasmodium falciparum reticulocyte binding protein homologue

The Plasmodium falciparum reticulocyte-binding-like protein homologue (RH) and erythrocyte binding-like (EBL) protein families play important roles during invasion, though their exact roles are not clear. Both EBL and RH proteins are thought to directly bind different receptors on the surface of the erythrocyte, and the binding properties for a number of EBLs and RHs have been described. While P. falciparum RH1 (PfRH1) and PfRH4 have been shown to act directly in two alternative invasion pathways used by merozoites, the functions of PfRH2a and PfRH2b during invasion are less defined. Here, using monoclonal antibodies raised against a unique region of PfRH2a, we show that PfRH2a moves from the rhoptry neck to the moving junction during merozoite invasion. The movement of PfRH2a to the junction is independent of the invasion pathway used by the merozoite, suggesting an additional function of the protein that is independent of receptor binding. We further show that PfRH2a is processed both in the schizont and during invasion, resulting in proteins with different erythrocyte binding properties. Our findings suggest that PfRH2a and, most likely, the other members of the RH family, depending on their processing stage, can engage different receptors at different stages of the invasion process.