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An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell


Coffey, MJ; Sleebs, BE; Uboldi, AD; Garnham, AL; Franco, M; Marino, ND; Panas, MW; Ferguson, DJ; Enciso, M; O'Neill, MT; Lopaticki, S; Stewart, RJ; Dewson, G; Smyth, GK; Smith, BJ; Masters, SL; Boothroyd, JC; Boddey, JA; Tonkin, CJ
2015-11-18
Elife
Journal Article in press
4
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 Deltaasp5 tachyzoites in vivo. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell.
eLife Sciences Publications
Infection and Immunity; Chemical Biology; Bioinformatics; Cell Signalling and Cell Death; Inflammation
10.7554/eLife.10809
26576949
Refer to copyright notice on published article.

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Creation Date 2015-11-25 02:39:38 Last Modified 2016-02-29 10:31:43