The parasitophorous vacuole membrane of toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy

Jayoung Choi, Sunmin Park, Scott B. Biering, Elizabeth Selleck, Catherine Y. Liu, Xin Zhang, Naonobu Fujita, Tatsuya Saitoh, Shizuo Akira, Tamotsu Yoshimori, L. David Sibley, Seungmin Hwang, Herbert W. Virgin

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    100 Citations (Scopus)

    Abstract

    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 invitro and invivo. In contrast, pharmacologic modulation of thedegradative 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 ontothe 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.

    Original languageEnglish
    Pages (from-to)924-935
    Number of pages12
    JournalImmunity
    Volume40
    Issue number6
    DOIs
    Publication statusPublished - 2014 Jun 19

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

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    Choi, J., Park, S., Biering, S. B., Selleck, E., Liu, C. Y., Zhang, X., Fujita, N., Saitoh, T., Akira, S., Yoshimori, T., Sibley, L. D., Hwang, S., & Virgin, H. W. (2014). The parasitophorous vacuole membrane of toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy. Immunity, 40(6), 924-935. https://doi.org/10.1016/j.immuni.2014.05.006