The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella.
The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella.
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DOI：
10.1091/mbc.e10-11-0893
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发表时间：
2011-07-01
影响因子：
3.3
通讯作者：
Yoshimori T
中科院分区：
文献类型：
--
作者：
Kageyama S;Omori H;Saitoh T;Sone T;Guan JL;Akira S;Imamoto F;Noda T;Yoshimori T
当沙门氏菌侵入哺乳动物上皮细胞时，一些群体被自噬蛋白LC3包围。我们发现LC3在沙门氏菌附近被招募，而不依赖于Atg9L1和FIP200，这是形成自噬体所必需的。ULK1复合物和Atg9L1的动态相互依赖。沙门氏菌发展成为上皮细胞中的常驻细菌，自噬机制（Atg）被认为在这一过程中起重要作用。在本文中，我们证明了一种类似自噬体的双膜结构围绕着沙门氏菌，仍然居住在含沙门氏菌液泡（SCV）内。这种双膜在200 kDa （FIP200）缺陷细胞的Atg9L1和FAK家族相互作用蛋白中存在缺陷。Atg9L1和FIP200对于磷脂酰肌醇3-激酶（PI3K）复合物的自噬特异性募集是重要的。然而，在缺乏Atg9L1、FIP200和PI3K复合体的情况下，LC3及其e3样酶Atg16L复合体仍然被沙门氏菌招募。我们认为LC3系统是通过一种独立于隔离膜生成的机制募集的。
When Salmonella invade mammalian epithelial cells, some populations are surrounded by the autophagy protein LC3. We found that LC3 was recruited in proximity to Salmonella independently of both Atg9L1 and FIP200, which are required for formation of autophagosomes. The dynamics of the ULK1 complex and Atg9L1 were dependent on one another. Salmonella develops into resident bacteria in epithelial cells, and the autophagic machinery (Atg) is thought to play an important role in this process. In this paper, we show that an autophagosome-like double-membrane structure surrounds the Salmonella still residing within the Salmonella-containing vacuole (SCV). This double membrane is defective in Atg9L1- and FAK family-interacting protein of 200 kDa (FIP200)-deficient cells. Atg9L1 and FIP200 are important for autophagy-specific recruitment of the phosphatidylinositol 3-kinase (PI3K) complex. However, in the absence of Atg9L1, FIP200, and the PI3K complex, LC3 and its E3-like enzyme, the Atg16L complex, are still recruited to Salmonella. We propose that the LC3 system is recruited through a mechanism that is independent of isolation membrane generation.