Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase
Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase
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DOI：
10.1016/j.celrep.2020.108107
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发表时间：
2020-09-08
期刊：
影响因子：
8.8
通讯作者：
Kubori, Tomoko
中科院分区：
文献类型：
--
作者：
Kitao, Tomoe;Taguchi, Kyoichiro;Kubori, Tomoko
胞内细菌病原体嗜肺军团菌利用细菌 IV 型分泌系统 (T4SS) 传递的许多效应蛋白来劫持早期分泌途径以建立其复制生态位，称为含军团菌 lla 的液泡 (LCV)。在 LCV 生物发生过程中，内质网 (ER) 囊泡可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (v-SNARE) Sec22b 是被招募到细菌吞噬体并与质膜上的靶膜 SNARE (t-SNARE) 形成非规范配对。在这里，我们鉴定了一种军团菌去泛素酶 (DUB) LotB，当异位表达时，它可以通过与外壳蛋白复合物 I (COPI) 囊泡相互作用来调节早期分泌途径。我们发现，Sec22b 在嗜肺军团菌感染后以 T4SS 依赖性方式泛素化，随后 LotB 从 Sec22b 中解离 K63 连接的泛素。 LotB 的 DUB 活性刺激 t-SNARE 语法蛋白 3 (Stx3) 从位于 LCV 上的 Sec22b 解离。我们的研究强调了一种利用细菌 DUB 来操纵感染诱导的 SNARE 配对动态的细菌策略。
The intracellular bacterial pathogen Legionella pneumophila uses many effector proteins delivered by the bacterial type IV secretion system (T4SS) to hijack the early secretory pathway to establish its replicative niche, known as the Legione lla-containing vacuole (LCV), On LCV biogenesis, the endoplasmic reticulum (ER) vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptors (v-SNARE) Sec22b is recruited to the bacterial phagosome and forms non-canonical pairings with target membrane SNAREs (t-SNAREs) from the plasma membrane. Here, we identify a Legionella deubiquitinase (DUB), LotB, that can modulate the early secretory pathway by interacting with coatomer protein complex I (COPI) vesicles when ectopically expressed. We show that Sec22b is ubiquitinated upon L. pneumophila infection in a T4SS-dependent manner and that, subsequently, LotB deconjugates K63-linked ubiquitins from Sec22b. The DUB activity of LotB stimulates dissociation of the t-SNARE syntaxin 3 (Stx3) from Sec22b, which resides on the LCV. Our study highlights a bacterial strategy manipulating the dynamics of infection-induced SNARE pairing using a bacterial DUB.