Parasite Replication Trigger

Abstract

Apicomplexan parasites, including Toxoplasma gondii and the malaria parasite Plasmodium falciparum , actively invade host cells. Little is known about the signals that govern initiation of replication once the parasite is intracellular. Apical membrane antigen 1 (AMA1) is released onto the parasite surface during invasion and cleaved by intramembrane proteolysis, mediated by a rhomboid-like serine protease, ROM4. Santos et al. (p. [473][1], published online 23 December; see the Perspective by [ Cowman and Tonkin ][2]) used conditional expression of Toxoplasma ROM4 to show that ROM4 activity is not essential for invasion, but instead is required for subsequent replication of the intracellular parasite. Furthermore, transgenic expression of the cleaved cytoplasmic tail of AMA1 alone—either from the Toxoplasma AMA1 or from its P. falciparum ortholog—completely restored the replicative capacity of the intracellular parasites. Thus, intramembrane cleavage of AMA1 is required to trigger parasite replication within the host cell. [1]: /lookup/doi/10.1126/science.1199284 [2]: /lookup/doi/10.1126/science.1201692