Immunity. 2014 Jun 11. pii: S1074-7613(14)00186-1. doi: 10.1016/j.immuni.2014.05.006. [Epub ahead of print]
The Parasitophorous Vacuole Membrane of Toxoplasma gondii Is Targeted for Disruption by Ubiquitin-like Conjugation Systems of Autophagy
Choi J1, Park S2, Biering SB3, Selleck E4, Liu CY2, Zhang X2, Fujita N5, Saitoh T6, Akira S6, Yoshimori T5, Sibley LD4, Hwang S7, Virgin HW8.
Autophagy is a lysosomal degradation pathway that is important in cellular homeostasis. Prior work showed a key role for the autophagy related 5 (Atg5) in resistance to Toxoplasma gondii. Here we show that the cassette of autophagy proteins involved in the conjugation of microtubule-associated protein 1 light chain 3 (LC3) to phosphatidylethanolamine, including Atg7, Atg3, and the Atg12-Atg5-Atg16L1 complex play crucial roles in the control of T. gondii in vitro and in vivo. In contrast, pharmacologic modulation of the degradative autophagy pathway or genetic deletion of other essential autophagy genes had no substantial effects. Rather the conjugation system was required for targeting of LC3 and interferon-γ effectors onto the vacuolar membrane of T. gondii and its consequent disruption. These data suggest that the ubiquitin-like conjugation systems that reorganize intracellular membranes during canonical autophagy are necessary for proper targeting of immune effectors to the intracellular vacuole membranes utilized by pathogens.
Copyright © 2014 Elsevier Inc. All rights reserved.
Copyright © 2014 Elsevier Inc. All rights reserved.
- PMID:
- 24931121
- [PubMed - as supplied by publisher]
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