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Home > Departments > Virology > Former team of the department > Stanislas TOMAVO : Molecular Cell Biology of Toxoplasma

Stanislas TOMAVO : Group Presentation

Toxoplasma gondii is a polarized single cell that contains unique secretory organelles, which release parasite-specific virulence factors that hijack many host functions. However, the mechanisms behind how the parasite traffics proteins and lipids to these organelles remain unknown. Our research intends to explore this problem using this model intracellular parasite

Team presentation

Apicomplexa include life-threatening intracellular parasites that have unusual secretory organelles, which are essential for host infection. A major outstanding problem in understanding the pathogenicity of Apicomplexa is to determine the biogenesis of secretory organelles named rhoptries, micronemes and dense granules (Figure 1). Toxoplasma gondii relies on transport vesicles that accurately deliver virulence-like factors named ROP, MIC and GRA proteins to secretory organelles that are required for host cell entry and hijacking of many host functions (Figure 1). However, our knowledge of the biochemical mechanisms underlying the biogenesis of such organelles remains quite incomplete, hindering our understanding of parasite infection. Therefore, deciphering how intracellular trafficking signals mediate high fidelity sorting into these intracellular compartments represents a central challenge.

Figure 1
Figure 1
Entry of Toxoplasma into the host cell requires the concerted actions of rhoptries, micronemes and dense granules that released ROP, MIC and GRA proteins for successful host invasion and hijacking of many biological functions.

Our team studies the mechanisms involved in intracellular trafficking and secretory organelle biogenesis in T. gondii. We uncovered that transport of proteins to these organelles requires a unique receptor named TgSORTLR for T. gondii Sortilin-Like Receptor (Figure 2). TgSORTLR resides in a non-conventional endosomal-like compartment (ELC) and recruits MIC and ROP proteins via its luminal region. Importantly, no rhoptries and micronemes were formed in the mutants lacking TgSORTLR, leading to a complete inhibition of host invasion and mice infection (Figure 2).

Figure 2
Figure 2
TgSORTLR functions require endosomal-like compartment and TgVSP35/retromer. Ablation of TgSORTLR and TgVSP35 led to the absence of secretory organelles and inhibition of infection.

We also demonstrated that the C-terminal tail of TgSORTLR is required for binding to the retromer Vps35-Vps29-Vps26 and recycling from Rab5 to Rab7-dependent ELC before its delivery back to Golgi. T. gondii Vps9, a guanine nucleotide exchange factor (GEF) that regulates Rab5 is also crucial for TgSORTLR function. Jointly, our findings unveiled that TgSORTLR, TgVps9 and retromer are essential for trafficking protein complexes into secretory organelles (Figure 3).

Figure 3
Figure 3
A novel strategy of merging the endosomal-like pathway and secretory systems for apical organelle biogenesis. The different regulators (X) remain to be determined.

Our progress in unraveling T. gondii intracellular trafficking inspired the idea that endosomal systems have been repurposed to form secretory organelles (Figure 3). However, the mechanisms involved in ECL formation remain largely incomplete.

We now envision using novel membrane binding factors as proof of concept that parasite-specific proteins can finely regulate protein and lipid trafficking during secretory organelle biogenesis. By combining biochemistry, cell and structural biology approaches, we aim:
1. To determine the structure of TgSORTLR-ligand complexes
2. To study lipid binding and membrane deformation during organelle biogenesis
3. To decipher functions of the late secretory vesicles that drive organelle formation
Because T. gondii is less complex than other mammalian systems, we expect to obtain mechanistic insights into how membrane interacting factors function in these parasites. As minute organisms branching off the eukaryotic lineage prior to the divergence of animals, fungi and plants, our studies may also provide new opportunities for therapeutic strategies.


Intracellular transport, Protein/lipid trafficking, Secretory organelle biogenesis, Host-Toxoplasma Interactions, Host Infection, Parasite virulence


TOMAVO Stanislas [Senior Researcher - CNRS]
Equipe Tomavo S. - Trafic Intracellulaire et Biogenèse des Organites chez Toxoplasma [Leader]
01 69 82 61 72 Orsay - Bât 400

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