title: Toxoplasma gondii targets a protein phosphatase 2C to the nuclei of infected host cells.
abstract: Intracellular pathogens have evolved a wide array of mechanisms to invade and co-opt their host cells for intracellular survival. Apicomplexan parasites such as Toxoplasma gondii employ the action of unique secretory organelles named rhoptries for internalization of the parasite and formation of a specialized niche within the host cell. We demonstrate that Toxoplasma gondii also uses secretion from the rhoptries during invasion to deliver a parasite-derived protein phosphatase 2C (PP2C-hn) into the host cell and direct it to the host nucleus. Delivery to the host nucleus does not require completion of invasion, as evidenced by the fact that parasites blocked in the initial stages of invasion with cytochalasin D are able to target PP2C-hn to the host nucleus. We have disrupted the gene encoding PP2C-hn and shown that PP2C-hn-knockout parasites exhibit a mild growth defect that can be rescued by complementation with the wild-type gene. The delivery of parasite effector proteins via the rhoptries provides a novel mechanism for Toxoplasma to directly access the command center of its host cell during infection by the parasite.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California--Los Angeles, Los Angeles, CA 90095-1489, USA.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Gilbert
authors.forename: Sandeep
authors.initials: S
authors.lastname: Ravindran
authors.forename: Jay M
authors.initials: JM
authors.lastname: Turetzky
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bradley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology* / Q000469:parasitology; D002478:Cells, Cultured; D006790:Host-Parasite Interactions; D006801:Humans; D008670:Metals / Q000737:chemistry; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014122:Toxoplasma / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal
chemical_list: D000913:Antibodies, Protozoan; D008670:Metals; D015800:Protozoan Proteins; C000607456:PPM1A protein, human; C000607457:PPM1B protein, human; C000607460:PPM1G protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C