A lipid-binding protein mediates rhoptry discharge and invasion in Plasmodium falciparum and Toxoplasma gondii parasites

Abstract

Members of the Apicomplexa phylum, including Plasmodium and Toxoplasma , have two types of secretory organelles (micronemes and rhoptries) whose sequential release is essential for invasion and the intracellular lifestyle of these eukaryotes. During invasion, rhoptries inject an array of invasion and virulence factors into the cytoplasm of the host cell, but the molecular mechanism mediating rhoptry exocytosis is unknown. Here we identify a set of parasite specific proteins, termed rhoptry apical surface proteins (RASP) that cap the extremity of the rhoptry. Depletion of RASP2 results in loss of rhoptry secretion and completely blocks parasite invasion and therefore parasite proliferation in both Toxoplasma and Plasmodium . Recombinant RASP2 binds charged lipids and likely contributes to assembling the machinery that docks/primes the rhoptry to the plasma membrane prior to fusion. This study provides important mechanistic insight into a parasite specific exocytic pathway, essential for the establishment of infection.

PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes

“…1a). The RNA expression profile and predicted SP of PfCERLI1 has led to speculation that it has a role in merozoite invasion that could be targeted by vaccines [16][17][18] . PfCERLI1 is highly conserved among Plasmodium spp., with >90% identity between P. falciparum, P. reichenowi and P. gaboni orthologues, >75% amino acid identity across human infecting species (including the zoonotic P. knowlesi) and >70% when compared to distantly related species (Fig.…”

“…Previous studies have identified PfCERLI1 (Pf3D7_0210600) as being a potential vaccine target on the basis of its predicted SP and late schizont stage of expression, a transcription profile typical of proteins involved in merozoite invasion 17,18 . In addition, PfCERLI1 was identified as a member of the 'invadome', an interaction network of putative invasion-associated proteins, and was localised to the merozoite apical tip in this study 16 .…”

“…A recent study by Suarez et al, 18 reported functional analysis of a homologue of PfCERLI1, which they termed Rhoptry Apical Surface Protein 2 (RASP2), in the related Apicomplexan parasite Toxoplasma gondii. They identified that TgRASP2 localises to the cytosolic face of the rhoptry, is essential for tachyzoite invasion of the host cell and confirmed that the C2 domain of this protein binds to the rhoptry membrane through interactions with phospholipids.…”

“…Thousands of daughter merozoites develop in the liver-stages and are released into the blood stream where they invade erythrocytes. In the case of P. falciparum, the blood-stage parasite multiplies over the next 48 h, forming [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] merozoites that rupture out of the schizont stage parasite and infect new erythrocytes 2 . This asexual blood-stage of the parasite lifecycle causes all disease symptoms.…”

Detection of the Rhoptry Neck Protein Complex in Plasmodium Sporozoites and Its Contribution to Sporozoite Invasion of Salivary Glands

“…cell invasion by Toxoplasma tachyzoites and Plasmodium merozoites, which was demonstrated by knockdown of a lipid binding protein, rhoptry apical surface protein 2, required for rhoptry protein secretion (1). Some proteins localized to the rhoptry neck region are inserted into the host cellular membrane as a complex prior to invasion and interact with a protein on the parasite membrane, apical membrane antigen 1 (AMA1), to form a moving junction between the parasite and target cells (2)(3)(4)(5).…”