An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell
- The Walter and Eliza Hall Institute of Medical Research, Australia
- Stanford University School of Medicine, United States
- University of Oxford, United Kingdom
- La Trobe University, Australia
- Walter and Eliza Hall Institute of Medical Research, Australia
Abstract
Infection by Toxoplasma gondii leads to massive changes to the host cell. Here we identify a novel host cell effector export pathway, which requires the Golgi-resident Aspartyl Protease 5 (ASP5). We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has similarity to the PEXEL-motif of Plasmodium parasites. We show that ASP5 matures substrates at both the N- and C-terminal ends of proteins and also controls trafficking of effectors without this motif. Furthermore, ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the vacuole. Assessment of host gene expression reveals that the ASP5-dependent pathway influences thousands of the transcriptional changes that Toxoplasma imparts on its host cell. All these changes result in attenuation of virulence of Δasp5 tachyzoites in vivo. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell.
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Author details
Ethics
Animal experimentation: All animal experiments complied with the regulatory standards of and were approved by the Walter and Eliza Hall Institute Animal Ethics Committees under approval number 2014.019.
Reviewing Editor
- Axel A Brakhage, Friedrich Schiller University Jena and Hans-Knöll-Institut, Germany
Version history
- Received: August 13, 2015
- Accepted: November 18, 2015
- Accepted Manuscript published: November 18, 2015 (version 1)
- Version of Record published: February 10, 2016 (version 2)
Copyright
© 2015, Coffey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell
eLife 4:e10809.
https://doi.org/10.7554/eLife.10809
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