Toxofilin upregulates the host cortical actin cytoskeleton dynamics facilitating Toxoplasma invasion

Abstract

Toxoplasma, a human pathogen and a model apicomplexan parasite, actively and rapidly invades host cells. To initiate invasion, the parasite induces the formation of a parasite-cell junction, progressively propels itself through the junction inside a newly formed vacuole that encloses the entering parasite. Litle is known how a few micron-large diameter parasite overcome the host cell cortical actin barrier to support these remarkably rapid process of internalization (< few seconds). Correlative light and electron microscopy in conjunction with electron tomography and three-dimensional image analysis indicate that toxofilin an actin-binding protein, secreted by invading parasites correlates with localized sites of disassembly of the host cell actin meshwork. Moreover, quantitative fluorescence speckle microscopy in cells expressing toxofilin indicates that toxofilin regulates actin filament disassembly and turnover. Furthermore, Toxoplasma tachyzoites lacking toxofilin, are impaired in cortical actin disassembly and exhibit delayed invasion kinetics. We propose that toxofilin locally upregulates actin turnover thus increasing depolymerization events at the site of entry that, in turn loosens the local host cell actin meshwork, facilitating parasite internalization and vacuole folding.