Pernas, Lena;
Boyle, Jon P.;
Fleckenstein, Martin A.;
Reese, Michael L.;
Konen-Waisman, Stephanie;
Howard, Jonathan C.;
Steinfeldt, Tobias;
Boothroyd, John C.
The intracellular parasite Toxoplasma injects polymorphic proteins into the host cell that subvert host defenses including recruitment of host mitochondria and membrane attack by p47 GTPases
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Media type:
E-Article
Title:
The intracellular parasite Toxoplasma injects polymorphic proteins into the host cell that subvert host defenses including recruitment of host mitochondria and membrane attack by p47 GTPases
Contributor:
Pernas, Lena;
Boyle, Jon P.;
Fleckenstein, Martin A.;
Reese, Michael L.;
Konen-Waisman, Stephanie;
Howard, Jonathan C.;
Steinfeldt, Tobias;
Boothroyd, John C.
Description:
<jats:p>The eukaryotic parasite, <jats:italic>Toxoplasma gondii</jats:italic>, is unusual in being able to infect almost any cell in almost any warm‐blooded animal. During invasion into the host cell, the parasite injects proteins that commandeer and/or subvert host functions. In this talk, I will describe the molecules Toxoplasma uses to recruit host mitochondria to the parasitophorous vacuolar membrane (PVM) within which the parasites divide. This recruitment has important consequences for how the host senses the parasite as well as for how the recruited mitochondria function. In the second part, I will describe how injected Toxoplasma kinases phosphorylate key host defense proteins, including a class of p47 GTPases encoded by the interferon‐gamma response genes (IRGs) that attack the PVM. Interestingly, this inactivation/phosphorylation is completely dependent on a family of injected pseudokinases that bind the IRGs and “present” them for phosphorylation by the active kinase. Our results on the structural features of these interactions will be discussed. Surprisingly, all of the parasite “effectors” involved in these processes differ between Toxoplasma strains resulting in major differences in their virulence. Speculative but plausible evolutionary reasons for these differences will be discussed.</jats:p>