STING induces LC3B lipidation onto single-membrane vesicles via the V-ATPase and ATG16L1-WD40 domain.
STING induces LC3B lipidation onto single-membrane vesicles via the V-ATPase and ATG16L1-WD40 domain.
复制标题
DOI：
10.1083/jcb.202009128
复制
发表时间：
2020-12-07
期刊：
影响因子：
--
通讯作者：
Youle RJ
中科院分区：
文献类型：
--
作者：
Fischer TD;Wang C;Padman BS;Lazarou M;Youle RJ
cGAS/STING途径的原始功能可能是诱导LC 3B脂化。Fischer等人显示cGAMP激活的STING诱导V-ATP酶募集ATG 16 L1以将LC 3B脂化到单膜核周囊泡上。细菌效应子SopF阻断了这一途径，表明在宿主防御中的作用。在哺乳动物细胞中检测到来自病毒或细菌感染的胞质双链DNA后，STING的环状二核苷酸活化诱导干扰素β表达以启动先天免疫防御。STING激活还诱导LC 3B脂质化，这是一种经典但不明确的自噬标志物，它促进了在干扰素途径进化之前出现的细胞自主抗病毒反应。我们报告说，STING激活诱导LC 3B脂化到单膜核周囊泡介导的ATG 16 L1通过其WD 40域，绕过规范的上游自噬机制的要求。这一过程被结合并抑制液泡ATP酶（V-ATP酶）的巴弗洛霉素A1和催化修饰V-ATP酶以通过ATG 16 L1抑制LC 3B脂化的细菌效应子SopF阻断。这些结果表明，cGAS-STING途径的激活诱导V-ATP酶依赖性LC 3B脂化，这可能介导细胞自主宿主防御，这是一种不同于LC 3B脂化到双膜自噬体上的意外机制。
A primordial function of the cGAS/STING pathway may be to induce LC3B lipidation. Fischer et al. show cGAMP-activated STING induces the V-ATPase to recruit ATG16L1 for lipidation of LC3B onto single-membrane perinuclear vesicles. The bacterial effector SopF blocks this pathway, suggesting roles in host defense. Following the detection of cytosolic double-stranded DNA from viral or bacterial infection in mammalian cells, cyclic dinucleotide activation of STING induces interferon β expression to initiate innate immune defenses. STING activation also induces LC3B lipidation, a classical but equivocal marker of autophagy, that promotes a cell-autonomous antiviral response that arose before evolution of the interferon pathway. We report that STING activation induces LC3B lipidation onto single-membrane perinuclear vesicles mediated by ATG16L1 via its WD40 domain, bypassing the requirement of canonical upstream autophagy machinery. This process is blocked by bafilomycin A1 that binds and inhibits the vacuolar ATPase (V-ATPase) and by SopF, a bacterial effector that catalytically modifies the V-ATPase to inhibit LC3B lipidation via ATG16L1. These results indicate that activation of the cGAS-STING pathway induces V-ATPase–dependent LC3B lipidation that may mediate cell-autonomous host defense, an unanticipated mechanism that is distinct from LC3B lipidation onto double-membrane autophagosomes.
登录
查看更多内容
影响因子：
28.3
作者：
通讯作者：
--
影响因子：
13.3
作者：
Jacquin E;Leclerc-Mercier S;Judon C;Blanchard E;Fraitag S;Florey O
通讯作者：
Florey O
DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
DOI：
10.1083/jcb.201304188
发表时间：
2013-10-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujita N;Morita E;Itoh T;Tanaka A;Nakaoka M;Osada Y;Umemoto T;Saitoh T;Nakatogawa H;Kobayashi S;Haraguchi T;Guan JL;Iwai K;Tokunaga F;Saito K;Ishibashi K;Akira S;Fukuda M;Noda T;Yoshimori T
通讯作者：
Yoshimori T
影响因子：
4
作者：
Heckmann, Bradlee L.;Green, Douglas R.
通讯作者：
Green, Douglas R.