Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites
Fig 6
A cartoon depicting invasion of (A) P. knowlesi or (B) P. falciparum merozoites into human erythrocytes.
P. knowlesi lacks an RH5-like molecule, resulting in the secretion of RIPR complexed with PkPTRAMP and PkCSS. The precise role of this complex in the invasion process is currently unknown but we speculate that PkPTRAMP as a transmembrane protein is both displaying PkRIPR and PkCSS on the merozoite surface after microneme release and is recognizing a receptor on the human erythrocyte, which is an important step required for successful invasion. BSG is not used as a human erythrocyte receptor by P. knowlesi. In stark contrast, P. falciparum RH5 and the micronemal proteins PfRIPR and PfCyRPA form a trimeric complex following rhoptry neck and microneme secretion. This complex localizes to the merozoite surface, through an interaction between the N-terminus of RH5 and GPI-anchored protein P113, and connects the parasite via BSG to the host erythrocyte. This interaction between RH5 and BSG is speculated to result in rhoptry bulb secretion and Ca2+ influx into the host cell. RH5 and RIPR have been postulated to multimerize and integrate into the erythrocyte membrane, which by an unknown mechanism results in the influx of Ca2+ into the host cell. This is followed by the formation of the moving junction. The RH5 complex follows the moving junction, from the apical tip of the merozoite to its posterior end, setting in motion the irreversible process of active invasion of the host cell by the merozoite.