Vacuolar Deconstruction

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Science  25 Nov 2005:
Vol. 310, Issue 5752, pp. 1247
DOI: 10.1126/science.310.5752.1247a

The protozoan parasite Toxoplasma gondiiactively invades host cells during infection and sets up house within a cytoplasmic structure known as a parasitophorous vacuole, created from the host cell plasma membrane. The host cells repel the invader, of course, and mice display an interferon-γ-induced cell autonomous immunity that depends on a class of GTPases: the p47 GTPases.

Martens et al. describe the mechanism of protection conferred by the p47 GTPases. These proteins appear to promote the disruption of the parasitophorous vacuole and the enclosed parasites. After invasion, several p47 GTPases accumulate in a GTP-dependent fashion on the parasitophorous vacuole membrane, which then suffers vesiculation, and eventually the vacuole and the parasite are destroyed. Elevated expression of the GTPases accelerates the disruption process, and inhibition of the GTPase activity by the expression of a dominant negative form interferes with interferon-γ-induced killing of the pathogen.

In a separate study, Bekpen et al. looked at the species distribution of p47 GTPases and explain why humans are more susceptible than mice to T. gondii infections. Humans express only a single form of the p47 GTPase, compared with more than 20 in the mouse, and it is not induced in response to interferon-γ hence, humans lack an innate form of defense against protozoan parasites. —SMH

PLoS Pathog. 1, e24 (2005); Genome Biol. 6, R92 (2005).

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