Dataset Information

Toxofilin upregulates the host cortical actin cytoskeleton dynamics, facilitating Toxoplasma invasion.

ABSTRACT: Toxoplasma gondii, 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, and progressively propels itself through the junction, inside a newly formed vacuole that encloses the entering parasite. Little is known about how a parasite that is a few microns in diameter overcomes the host cell cortical actin barrier to achieve the remarkably rapid process of internalization (less than a few seconds). Using correlative light and electron microscopy in conjunction with electron tomography and three-dimensional image analysis we identified 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 of cells expressing toxofilin showed that toxofilin regulates actin filament disassembly and turnover. Furthermore, Toxoplasma tachyzoites lacking toxofilin, were found to be impaired in cortical actin disassembly and exhibited 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.

SUBMITTER: Delorme-Walker V

PROVIDER: S-EPMC3516439 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Toxofilin upregulates the host cortical actin cytoskeleton dynamics, facilitating Toxoplasma invasion.

Delorme-Walker Violaine V Abrivard Marie M Lagal Vanessa V Anderson Karen K Perazzi Audrey A Gonzalez Virginie V Page Christopher C Chauvet Juliette J Ochoa Wendy W Volkmann Niels N Hanein Dorit D Tardieux Isabelle I

Journal of cell science 20120528 Pt 18

Toxoplasma gondii, 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, and progressively propels itself through the junction, inside a newly formed vacuole that encloses the entering parasite. Little is known about how a parasite that is a few microns in diameter overcomes the host cell cortical actin barrier to achieve the remarkably rapid process of internalization (le ...[more]

PMID: 22641695

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Project description:Apicomplexan parasites actively invade host cells using a mechanism predicted to be powered by a parasite actin-dependent myosin motor. In the model apicomplexan Toxoplasma gondii, inducible knockout of the actin gene, ACT1, was recently demonstrated to limit but not completely abolish invasion. This observation has led to the provocative suggestion that T. gondii possesses alternative, ACT1-independent invasion pathways. Here, we dissected the residual invasive ability of ?act1 parasites. Surprisingly, we were able to detect residual ACT1 protein in inducible ?act1 parasites as long as 5 days after ACT1 deletion. We further found that the longer ?act1 parasites were propagated after ACT1 deletion, the more severe an invasion defect was observed. Both findings are consistent with the quantity of residual ACT1 retained in ?act1 parasites being responsible for their invasive ability. Furthermore, invasion by the ?act1 parasites was also sensitive to the actin polymerization inhibitor cytochalasin D. Finally, there was no clear defect in attachment to host cells or moving junction formation by ?act1 parasites. However, ?act1 parasites often exhibited delayed entry into host cells, suggesting a defect specific to the penetration stage of invasion. Overall, our results support a model where residual ACT1 protein retained in inducible ?act1 parasites facilitates their limited invasive ability and confirm that parasite actin is essential for efficient penetration into host cells during invasion.The prevailing model for apicomplexan invasion has recently been suggested to require major revision, based on studies where core components of the invasion machinery were genetically disrupted using a Cre-Lox-based inducible knockout system. For the myosin component of the motor thought to power invasion, an alternative parasite myosin was recently demonstrated to functionally compensate for loss of the primary myosin involved in invasion. Here, we highlight a second mechanism that can account for the surprising ability of parasites to invade after genetic disruption of core invasion machinery. Specifically, residual actin protein present in inducible knockout parasites appears able to support their limited invasion of host cells. Our results have important implications for the interpretation of the apicomplexan invasion model and also highlight significant considerations when analyzing the phenotypes of inducible knockout parasites generated using Cre-Lox technology.

Dataset Information

Toxofilin upregulates the host cortical actin cytoskeleton dynamics, facilitating Toxoplasma invasion.

Publications

Toxofilin upregulates the host cortical actin cytoskeleton dynamics, facilitating Toxoplasma invasion.

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