A Critical Role for Toxoplasma gondii Vacuolar Protein Sorting VPS9 in Secretory Organelle Biogenesis and Host Infection

Takaya Sakura, Fabien Sindikubwabo, Lena K. Oesterlin, Hugo Bousquet, Christian Slomianny, Mohamed-Ali Hakimi, Gordon Langsley & Stanislas Tomavo

Scientific report 2016 Dec 14; 6:38842

Speaker: Po-Liang, Chu (朱珀亮)                                        Time: 15:00~16:00, Mar 1 2017

Commentator: Dr. Wei-Chen, Lin (林威辰 老師)               Place: Room 601

Abstract:

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. This obligate intracellular parasite can infect humans as well as virtually all warm-blooded animals, including mammals and birds. Rhoptries, micronemes, and dense granules, which are secretory organelles unique toToxoplasma and other apicomplexan parasites, play critical roles in parasite invasion. It is now well established that apicomplexan parasites operate an unconventional endosome-like system (ELC) to traffic proteins from the Golgi apparatus to rhoptries and micronemes.[1] However, the mechanisms involved in endosome-like vesicle formation and delivery to these organelles in general remain elusive. Here, the authors report that the TgVps9 protein is a Rab5 GTP-Exchange Factor (GEF) that is crucial for ROP protein maturation and processing, and its loss leads to a reduced number of rhoptries. Absence of TgVps9 also impairs peripheral microneme biogenesis and disturbs dense granule secretion resulting in an accumulation of novel vesicles present both within and outside the parasite. Then, authors observed a significant mis-sorting of rhoptry, microneme and dense granule proteins and found an accumulation of unprocessed ROP proteins such as ROP2 and ROP4 following the loss of TgVps9. Authors also found in the conditional TgVps9 mutants that the typical conical microneme M2AP and MIC3 signals were completely changed to fluorescence signals at the extreme tip of each TgVps9-depleted mutant. Finally, the iKOTgVps9 mutants were severely impaired in their ability to invade host cells with an 80% decrease. In conclusion, loss of TgVps9 inhibits rhoptry protein processing/maturation, impairs secretory organelle biogenesis and secretion, leading to an inability of TgVps9-deficient mutants to invade host cells.

Reference:

1.    Jimenez-Ruiz, E., Morlon-Guyot, J., Daher, W. & Meissner, M. Vacuolar protein sorting mechanisms in apicomplexan parasites. Mol. Biochem. Parasitol, doi: 10.1016/j.molbiopara.2016.01.007 (2016).