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The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance.
- Source :
-
PloS one [PLoS One] 2014 Jan 17; Vol. 9 (1), pp. e86684. Date of Electronic Publication: 2014 Jan 17 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps). Members of these two GTPase families associate with pathogen-containing vacuoles (PVs) and solicit antimicrobial resistance pathways specifically to the intracellular site of infection. The proper delivery of IRG and Gbp proteins to PVs requires the autophagy factor Atg5. Atg5 is part of a protein complex that facilitates the transfer of the ubiquitin-like protein Atg8 from the E2-like conjugation enzyme Atg3 to the lipid phosphatidylethanolamine. Here, we show that Atg3 expression, similar to Atg5 expression, is required for IRG and Gbp proteins to dock to PVs. We further demonstrate that expression of a dominant-active, GTP-locked IRG protein variant rescues the PV targeting defect of Atg3- and Atg5-deficient cells, suggesting a possible role for Atg proteins in the activation of IRG proteins. Lastly, we show that IFN-induced cell-autonomous resistance to C. trachomatis infections in mouse cells depends not only on Atg5 and IRG proteins, as previously demonstrated, but also requires the expression of Atg3 and Gbp proteins. These findings provide a foundation for a better understanding of IRG- and Gbp-dependent cell-autonomous resistance and its regulation by Atg proteins.
- Subjects :
- Animals
Autophagy-Related Protein 5
Autophagy-Related Proteins
Chlamydia Infections immunology
Chlamydia Infections metabolism
Chlamydia Infections pathology
Chlamydia trachomatis drug effects
Chromosomes, Mammalian metabolism
Guanosine Triphosphate metabolism
Inclusion Bodies drug effects
Inclusion Bodies metabolism
Interferon-gamma pharmacology
Mice
Microtubule-Associated Proteins deficiency
Microtubule-Associated Proteins metabolism
Mutant Proteins metabolism
Protein Binding drug effects
Toxoplasma drug effects
Toxoplasmosis immunology
Toxoplasmosis metabolism
Toxoplasmosis pathology
Ubiquitin-Conjugating Enzymes deficiency
Vacuoles drug effects
Chlamydia trachomatis metabolism
Disease Resistance drug effects
GTP-Binding Proteins metabolism
Immunity drug effects
Toxoplasma metabolism
Ubiquitin-Conjugating Enzymes metabolism
Vacuoles metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24466199
- Full Text :
- https://doi.org/10.1371/journal.pone.0086684