title: Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode.
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.
authors.affiliation: Department of Microbiology, Faculty of Medicine, University of Geneva, 1 rue-Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Santos
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blackman
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
mesh_terms: D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009068:Movement; D050505:Mutant Proteins / Q000378:metabolism; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014122:Toxoplasma / Q000166:cytology / Q000254:growth & development / Q000502:physiology*
chemical_list: C506564:AMA1 protein, Toxoplasma gondii; D000953:Antigens, Protozoan; D008565:Membrane Proteins; D050505:Mutant Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D057057:Serine Proteases