Elucidation of functional significance of plasmodium falciparum reticulocyte binding like protein homologues - RH1, RH2A AND RH4 during merozoite invasion.
Date of Issue2012
School of Biological Sciences
The successful invasion of Plasmodium falciparum depends on the recognition of host cell receptors by parasite ligands. One major family of ligands involved in these interactions is the Reticulocyte binding like protein Homologues (RHs). Using highly specific monoclonal antibodies against PfRH1, RH2a and RH4, we have focused on the processing and erythrocyte binding properties of RHs that are important for host cell recognition. Significantly, by live video and confocal microscopy, we identified that these PfRHs are important for merozoite-erythrocyte junction formation. Furthermore, using proximity ligation assay and co-immunoprecipitation, we demonstrate that PfRH1, RH2a and RH4 interact with each other to enable erythrocyte invasion. Interestingly, we observed a combinatorial inhibitory effect when antibodies against different PfRHs are used during merozoite invasion. Hence, our data indicate that cocktail of antibodies against various PfRH ligands can be used for malaria intervention. Taken together, our investigations on PfRHs provide new insights on how the parasite successfully invades the host cell.