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

Science. 2010 Dec 23. [Epub ahead of print]

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

Santos JM, Ferguson DJ, Blackman MJ, Soldati-Favre D.

Department of Microbiology, Faculty of Medicine, University of Geneva, 1 rue-Michel Servet, 1211 Geneva 4, Switzerland.

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.

PMID: 21205639 [PubMed - as supplied by publisher]