An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell
AuthorCoffey, MJ; Sleebs, BE; Uboldi, AD; Garnham, A; Franco, M; Marino, ND; Panas, MW; Ferguson, DJP; Enciso, M; O'Neill, MT; ...
PublisherELIFE SCIENCES PUBLICATIONS LTD
University of Melbourne Author/sDewson, Grant; Uboldi, Alessandro; Tonkin, Christopher; Sleebs, Brad; Boddey, Justin; Masters, Seth; Smyth, Gordon; Stewart, Rebecca; Coffey, Michael; Garnham, Alexandra; ...
AffiliationMedical Biology (W.E.H.I.)
School of Mathematics and Statistics
Document TypeJournal Article
CitationsCoffey, M. J., Sleebs, B. E., Uboldi, A. D., Garnham, A., Franco, M., Marino, N. D., Panas, M. W., Ferguson, D. J. P., Enciso, M., O'Neill, M. T., Lopaticki, S., Stewart, R. J., Dewson, G., Smyth, G. K., Smith, B. J., Masters, S. L., Boothroyd, J. C., Boddey, J. A. & Tonkin, C. J. (2015). An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell. ELIFE, 4 (NOVEMBER2015), https://doi.org/10.7554/eLife.10809.
Access StatusOpen Access
Infection by Toxoplasma gondii leads to massive changes to the host cell. Here, we identify a novel host cell effector export pathway that 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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