Sabrina MARION et Mathieu GISSOT

Biologie Moléculaire et Cellulaire de Toxoplasma gondii

Toxoplasma gondii provides a convenient bridge for understanding the architecture of even more highly simplified organisms with the ease to interpret in morphological terms, and for which genetic experiments are also feasible. The parasite is completely tailored for the recognition and invasion of host cells and can be identified by the apical complex consisting of secretory organelles named micronemes (MIC) and rhoptries (ROP). These organelles are released sequentially during host cell entry and invasion. T. gondii ROP and MIC proteins navigate through the ER, Golgi and endosome-like organelles prior to being packaged into their respective apical secretory organelles. However, very few of these factors have been characterized and precisely how proteins are guided through the parasite’s endomembranous structures remains poorly understood. Therefore, elucidation of mechanisms involved in protein trafficking and organelle biogenesis in T. gondii could provide a unique glimpse into a “simplified” sorting system in lower eukaryotes and opens the possibility of exploiting protein-dependent trafficking for controlling parasitic infections. We have recently reported that a Toxoplasma gondii Sortilin-Like Receptor named TgSORTLR, a type I transmembrane receptor localized in the Golgi cisternae and proximal vesicles of the parasite acts as a cargo receptor likely involved in retrograde and/or anterograde transport, and that the protein is necessary for the biogenesis of secretory organelles. The first purpose of our work is to provide a cellular and an in vivo functional assay system, which will be helpful to decipher protein trafficking involving TgSORTLR, a sortilin-like protein, and TgSORTLR-associated trafficking factors that play crucial role in the biogenesis of key apical secretory organelles of T. gondii. We conclude that the parasite may have evolved a novel strategy of merging endosomal and secretory systems to take advantage of endosomal proteases for activation of regulated secretory products. These data also lay the foundation for future works dissecting the mechanism of sortilin-based protein trafficking. Our second purpose is to discover the crucial factors controlling the packaging of rhoptries and micronemes proteins into their corresponding organelles known to be essential for host invasion, parasite virulence and differentiation.

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