期刊
AUTOPHAGY
卷 12, 期 7, 页码 1153-1167出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1178447
关键词
autophagy; GBP; IFN; IRG; LC3; TAG; targeting; Toxoplasma gondii; ubiquitin
类别
资金
- Cancer Research Foundation
- Institutional Research Grant from the American Cancer Society [IRG-58-004-53-IRG]
- University of Chicago Comprehensive Cancer Center Support Grant [P30 CA14599]
- University of Chicago Digestive Diseases Research Core Center [NIDDK P30DK42086]
- Cancer Center Core facilities
- Molecular and Cellular Biology Training Grant [T32 GM007183]
LC3 has been used as a marker to locate autophagosomes. However, it is also well established that LC3 can localize on various membranous structures other than autophagosomes. We recently demonstrated that the LC3 conjugation system (ATG7, ATG3, and ATG12-ATG5-ATG16L1) is required to target LC3 and IFNG (interferon, gamma)-inducible GTPases to the parasitophorus vacuole membrane (PVM) of a protist parasite Toxoplasma gondii and consequently for IFNG to control T. gondii infection. Here we show that not only LC3, but also its homologs (GABARAP, GABARAPL1, and GABARAPL2) localize on the PVM of T. gondii in a conjugation-dependent manner. Knockout/knockdown of all LC3 homologs led to a significant reduction in targeting of the IFNG-inducible GTPases to the PVM of T. gondii and the IFNG-mediated control of T. gondii infection. Furthermore, when we relocated the ATG12-ATG5-ATG16L1 complex, which specifies the conjugation site of LC3 homologs, to alternative target membranes, the IFNG-inducible GTPases were targeted to the new target membranes rather than the PVM of T. gondii. These data suggest that the localization of LC3 homologs onto a membrane by the LC3 conjugation system is necessary and sufficient for targeting of the IFNG-inducible GTPases to the membrane, implying Targeting by AutophaGy proteins (TAG). Our data further suggest that the conjugation of ubiquitin-like LC3 homologs to the phospholipids of membranes may change the destiny of the membranes beyond degradation through lysosomal fusion, as the conjugation of ubiquitin to proteins changes the destiny of the proteins beyond proteasomal degradation.
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