Toxoplasma membrane inositol phospholipid binding protein TgREMIND is essential for secretory organelle function and host infection.

Apicomplexan parasites possess specialized secretory organelles called rhoptries, micronemes, and dense granules that play a vital role in host infection. In this study, we demonstrate that TgREMIND, a protein found in Toxoplasma gondii, is necessary for the biogenesis of rhoptries and dense granules. TgREMIND contains a Fes-CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain, which binds to membrane phospholipids, as well as a novel uncharacterized domain that we have named REMIND (regulator of membrane-interacting domain).

An image-based high-content screening for compounds targeting repurposed inhibitors effective against the malaria parasite .

phylum includes numerous obligate intracellular protozoan parasites that are life threatening for humans and animals. In this context, and are of particular interest, as they are responsible for malaria and toxoplasmosis, respectively, for which efficient vaccines are presently lacking and therapies need to be improved. Apicomplexan parasites have a highly polarized morphology, with their apical end containing specific secretory organelles named rhoptries and micronemes, which depend on the unique receptor and transporter sortilin TgSORT for their biogenesis.

The luminal domain of sortilin adopts a ring-shaped structure exhibiting motifs specific to apicomplexan parasites.

Rhoptries and micronemes are essential for host cell invasion and survival of all apicomplexan parasites, which are composed of numerous obligate intracellular protozoan pathogens including (malaria) and (toxoplasmosis) that infect humans and animals causing severe diseases. We identified SORT as an essential cargo receptor, which drives the transport of rhoptry (ROP) and microneme (MIC) proteins to ensure the biogenesis of these secretory organelles. The luminal domain of 752 amino acid long situated at the N-terminus end of TgSORT has been described to bind to MIC and ROP proteins.

A noncanonical autophagy is involved in the transfer of -microvesicles to astrocytes.

Cerebral malaria is a neuroinflammatory disease induced by infection. In animal models, the neuro-pathophysiology of cerebral malaria results from the sequestration of infected red blood cells (iRBCs) in microvessels that promotes the activation of glial cells in the brain. This activation provokes an exacerbated inflammatory response characterized by the secretion of proinflammatory cytokines and chemokines, leading to brain infiltration by pathogenic CD8 T lymphocytes.

The dense granule protein TgGRA3 interacts with host Golgi and dysregulates anterograde transport.

After entry into the host cell, the intracellular parasite resides within a membrane-bound compartment, the parasitophorous vacuole (PV). The PV defines an intracellular, parasite-specific niche surrounded by host organelles, including the Golgi apparatus. The mechanism by which hijacks the host Golgi and subverts its functions remains unknown.