Parasite Replication Trigger

Science Signaling  01 Feb 2011:
Vol. 4, Issue 158, pp. ec34
DOI: 10.1126/scisignal.4158ec34

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. (see the Perspective by Cowman and Tonkin) 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.

J. M. Santos, D. J. P. Ferguson, M. J. Blackman, D. Soldati-Favre, Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode. Science 331, 473–477 (2011). [Abstract] [Full Text]

A. F. Cowman, C. J. Tonkin, A tail of division. Science 331, 409–410 (2011).[Abstract] [Full Text]