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Pfcerli2, a duplicated gene in the malaria parasite Plasmodium falciparum essential for invasion of erythrocytes as revealed by phylogenetic and cell biological analysis.

ABSTRACT: 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, a related cytosolically exposed rhoptry bulb protein. 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 after formation of the tight junction. PfCERLI2 knockdown was associated with inhibition of rhoptry antigen processing and a significant elongation of the rhoptries, suggesting that the inability of merozoites to invade is caused by aberrant rhoptry function due to PfCERLI2 deficiency. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Plasmodium Falciparum Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Ghizal Siddiqui

LAB HEAD: Danny Wilson

PROVIDER: PXD028937 | Pride | 2021-11-15

REPOSITORIES: Pride

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