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Fanou, L. A.

Publications and source records attributed to Fanou, L. A..

2 recordsLinked to original sources

Toxoplasma Membrane Inositol Phospholipid Binding Protein TgREMIND Is Essential for Secretory Organelle Function and Host Infection

Apicomplexan parasites have specialized secretory organelles called rhoptries, micronemes, and dense granules that are essential for host infection. Here, we show that TgREMIND, a Toxoplasma gondii protein containing a membrane phospholipid interacting domain, is required for the biogenesis of rhoptries and dense granules. TgREMIND contains a Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain at the N-terminus, known to promote cell membrane bending, and a novel uncharacterized domain that we named REMIND for regulator of membrane interacting domain at the C-terminus. TgREMIND binds to PIP2 lipid species and both F-BAR and REMIND domains are necessary to ensure proper biological activities in vitro and in cellulo. Conditional depletion of TgREMIND results in the absence of dense granules and abnormal transparent rhoptries, leading to a severe inhibition of parasite motility, host invasion, and dissemination. Thus, our study demonstrates that TgREMIND is essential for the proper functioning of key secretory organelles required for successful infection by Toxoplasma.

cell biology↗

Structural analysis of Toxoplasma gondii sortilin

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 Plasmodium falciparum (malaria) and Toxoplasma gondii (toxoplasmosis) that infect humans and animals causing severe diseases. We identified Toxoplasma gondii TgSORT 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 ectodomain of 752 amino acid long situated at the N-terminus end of TgSORT has been described to bind to MIC and ROP proteins. Here, we present an optimized protocol for expression of the entire luminal ectodomain of TgSORT (Tg-NSORT) in the yeast Pichia pastoris. Optimization of its coding sequence, cloning and transformation of the yeast P. pastoris allowed the secretion of Tg-NSORT. The protein was purified and further analyzed by negative staining electron microscopy. In addition, molecular modeling using AlphaFold identified key differences between human and T gondii sortilin. The structural features that are only present in T. gondii and other apicomplexan parasites were highlighted. Elucidating the roles of these specific structural features may be useful for designing new therapeutic agents against apicomplexan parasites

cell biology↗