A pan‐apicomplexan phosphoinositide‐binding protein acts in malarial microneme exocytosis

Abstract

Invasion of human red blood cells by the malaria parasite Plasmodium falciparum is an essential step in the development of the disease. Consequently, the molecular players involved in host cell invasion represent important targets for inhibitor design and vaccine development. The process of merozoite invasion is a succession of steps underlined by the sequential secretion of the organelles of the apical complex. However, little is known with regard to how their contents are exocytosed. Here, we identify a phosphoinositide‐binding protein conserved in apicomplexan parasites and show that it is important for the attachment and subsequent invasion of the erythrocyte by the merozoite. Critically, removing the protein from its site of action by knock sideways preferentially prevents the secretion of certain types of micronemes. Our results therefore provide evidence for a role of phosphoinositide lipids in the malaria invasion process and provide further insight into the secretion of microneme organelle populations, which is potentially applicable to diverse apicomplexan parasites.

Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

“…These two subsets differ in their composition and involve distinct trafficking pathways (Matthiesen et al, 2001; Morlon‐Guyot et al, 2018). Differential localization and/or secretion of the micronemal proteins AMA1 and EBA175 has also been reported in P. falciparum merozoites, consistent with the existence of distinct microneme subtypes also in Plasmodium (Absalon et al, 2018; Ebrahimzadeh et al, 2019; Healer et al, 2002).…”

“…Distinct extrinsic stimuli may initiate successive cGMP and/or cAMP signals. Alternatively, distinct downstream effectors, including Ca 2+ ‐dependent enzymes or proteins that target micronemes to the plasma membrane for exocytosis (Bullen et al, 2016; Dubois & Soldati‐Favre, 2019; Ebrahimzadeh et al, 2019), may selectively trigger secretion of “migration‐specific” or “invasion‐specific” microneme subsets.…”

Pfcerli2, a duplicated gene in the malaria parasitePlasmodium falciparumessential for invasion of erythrocytes as revealed by phylogenetic and cell biological analysis

“…The distance between the basal end of the nucleus (DAPI signal) and the RAP1 or RON4 foci was measured as described previously 55 . Images were first blinded and then using the Plot Profile plugin on FIJI, a line was drawn from the basal extremity of the DAPI signal through the RAP1 and RON4 foci to generate intensity profiles for the three markers as a function of distance of the line.…”

A Phosphoinositide-Binding Protein Acts in the Trafficking Pathway of Hemoglobin in the Malaria Parasite Plasmodium falciparum

“…The parasite’s PI-PLC homologue, through its degradation of PI(4,5)P 2 into IP3 and diacylglycerol and the subsequent release of intracellular calcium stores, is important in numerous processes such as gametocyte activation ( 25 – 27 ), ookinete and sporozoite motility, and merozoite egress ( 28 , 29 ). P. falciparum PPI-binding proteins have been implicated in processes such as merozoite invasion ( 30 – 32 ) and the cell cycle ( 33 ).…”