Intramembrane Cleavage of AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode

Joana M. Santos, David J. P. Ferguson, Michael J. Blackman, Dominique Soldati-Favre1. Science 331, 473 (2011)

Student: Yung-Han Yang (楊詠涵)                                Time:15: 00~16:00 Apr. 27, 2011

Commentator: Dr. Chih-Li Hsu (胥直利老師)             Place: Room 601

Abstract

Apicomplexan parasites are an important group of single-celled pathogens which includes Toxoplasma gondii, the causative agent of toxoplasmosis. These parasites actively invade host cells and then divide within them. T. gondii can invade virtually any cell and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. A protein called apical membrane antigen 1 (AMA1) is crucial for invasion in both Toxoplasma and Plasmodium falciparum, a kind of malaria parasite. They used a conditional expression system to show that over-expression of a dominant-negative form of the rhomboid enzyme (called ROM4) produced a severe defect in parasite replication. This defect could be completely overcome by expression of the cytoplasmic ‘tail’ of AMA1 from either Toxoplasma or Plasmodium falciparum. The results suggest that the action of ROM4 on AMA1 provides the signal to the intracellular parasite to begin replication. Progression of the diseases caused byapicomplexan parasites absolutely requires that they multiply within infected individuals, but prior to this work we had no clues as to how they are triggered to start replicating following invasion. This work provides the very first information on the regulation of this important aspect of the parasite life cycle.

References

1. Jeffrey Mital. et al. (2005) Conditional Expression of Toxoplasma gondii Apical Membrane Antigen-1 (TgAMA1) Demonstrates That TgAMA1 Plays a Critical Role in Host Cell Invasion. Mol. Biol.Cell 16, 4341
2. J. S. Buguliskis. et al. (2010) Rhomboid 4 (ROM4) Affects the Processing of Surface Adhesins and Facilitates Host Cell Invasion by Toxoplasma gondii. PLoS Pathogens. 6, e1000858