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Science 331 (6016): 473-477

Copyright © 2011 by the American Association for the Advancement of Science

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

Joana M. Santos,1,3 David J. P. Ferguson,2 Michael J. Blackman,3 Dominique Soldati-Favre1,*

Abstract: Apicomplexan parasites invade host cells 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. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.

1 Department of Microbiology, Faculty of Medicine, University of Geneva, 1 rue-Michel Servet, 1211 Geneva 4, Switzerland.
2 Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
3 Division of Parasitology, Medical Research Council National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

* To whom correspondence should be addressed. E-mail: Dominique.Soldati-Favre{at}

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