Toxo PP2C targets host cell nucleus

Eukaryot Cell. 2006 Nov 3; [Epub ahead of print]

Toxoplasma gondii Targets a Protein Phosphatase 2C to the Nucleus of Infected Host Cells.

Gilbert LA, Ravindran S, Turetzky JM, Boothroyd JC, Bradley PJ.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles CA 90095-1489 USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124 USA.

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 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. 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.