Format

Send to

Choose Destination
Elife. 2015 Nov 18;4. pii: e10809. doi: 10.7554/eLife.10809.

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

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
2
Department of Medical Biology, The University of Melbourne, Melbourne, Australia.
3
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States.
4
Nuffield Department of Clinical Laboratory Science, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom.
5
La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
6
Department of Mathematics and Statistics, The University of Melbourne, Melbourne, Australia.

Abstract

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.

KEYWORDS:

Toxoplasma; effector; export; infectious disease; microbiology; protease

PMID:
26576949
PMCID:
PMC4764566
DOI:
10.7554/eLife.10809
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center