Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites.

Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.

The Ins and Outs of Plasmodium Rhoptries, Focusing on the Cytosolic Side.

Parasites of the genus Plasmodium cause human and animal malaria, leading to significant health and economic impacts. A key aspect of the complex life cycle of Plasmodium parasites is the invasion of the parasite into its host cell, which is mediated by secretory organelles. The largest of these organelles, the rhoptry, undergoes rapid and profound physiological changes when it secretes its contents during merozoite and sporozoite invasion of the host erythrocyte and hepatocyte, respectively. Here we discuss recent advancements in our understanding of the dynamic rhoptry biology during the parasite's invasive stages, with a focus on the roles of cytosolically exposed rhoptry-interacting proteins (C-RIPs). We explore potential similarities between the molecular mechanisms driving merozoite and sporozoite rhoptry function.