Functional insight the role of plasmodium falciparum reticulocyte blinding like protein homologues : RH2B and RH5 during merozoites invasion

Abstract

The process of Plasmodium merozoites invasion is a complex multi-step process. In understanding the mechanisms leading to successful merozoites invasion, a group of proteins known as Plasmodium falciparum erythrocyte binding ligands as well as Plasmodium falciparum reticulocyte binding - like protein homologues (PfRH) have been shown to be necessary. These proteins have been shown to play a role in sensing the erythrocyte. Of the PfRH family, it is becoming clearer of their ability to affect the secretion of microneme proteins which are necessary to establish the tight junction. In this presentation, the role of PfRH2b during merozoite invasion has studied. Like PfRH1, PfRH2b has been shown to regulate the increase in merozoites Ca2+. This, we have shown to affect the release of EBA175 to the erythrocyte surface. Our data also points to the fact that the secretion of EBA175 to the surface is more prominent when the merozoites are engaged with the RBCs. Furthermore we have provided the detailed processing events that occur in the PfRH2b protein before and during merozoites invasion. Functional insight on RH5-Basigin interaction has been provided. In this, we have shown RH5 to be involved in invasion independent of EBA175 surface expression but functions before tight junction formation. We have provided evidence of RH5-Basigin interaction driving Ca2+ in the RBC leading to the remodelling of the RBC cytoskeletal proteins arrangement. We have confirmed that recombinant RH5 has the ability to induce changes in the RBC cytoskeleton upon binding. This mechanism we propose facilitates the insertion of AMA1-RON complex into the RBC membrane leading to tight junction formation. This knowledge we believe will help in advancing our understanding as well as provide avenue to explore the mechanisms of merozoites invasion