Elife. 2015 Nov 18;4. pii: e10809. doi: 10.7554/eLife.10809. [Epub ahead of print]
Coffey MJ1,
Sleebs BE1,
Uboldi AD1,
Garnham AL1,
Franco M2,
Marino ND2,
Panas MW2,
Ferguson DJ3,
Enciso M4,
O'Neill MT1,
Lopaticki S1,
Stewart RJ1,
Dewson G1,
Smyth GK1,
Smith BJ4,
Masters SL1,
Boothroyd JC2,
Boddey JA1,
Tonkin CJ5.
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.
KEYWORDS:
infectious disease; microbiology
- PMID:
- 26576949
- [PubMed - as supplied by publisher]
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