Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes.
Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes.
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DOI：
10.1038/ncb2363
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发表时间：
2011-10-16
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
自噬蛋白通常参与介导大量细胞质和细胞器降解的双膜自噬体的形成。在这里，我们报告的修改单膜空泡细胞的自噬蛋白。轻链3（LC 3）是自噬体的一种组分，以依赖于脂化机制（包括Atg 5和Atg 7）和III类PI-3-激酶Vps 34的方式被募集到单膜内吞空泡、巨胞饮体和携带凋亡细胞的吞噬体。自噬机制的这些下游组分，而不是上游mTOR调节的Ulk-Atgl 3-Fip 200复合物，促进溶酶体融合成单膜和内化货物的降解。对于内吞，一种活细胞吞噬程序，溶酶体与空泡膜的自噬蛋白依赖性融合导致内化细胞的死亡，内化细胞被其宿主杀死。由于含有病原体的吞噬体可以以类似的方式被靶向，因此上皮细胞通过这种机制的死亡模拟病原体破坏。这些数据将单膜空泡的靶向定义为在不存在病原生物的情况下细胞中自噬途径蛋白的性质。
Autophagy proteins are normally involved in the formation of double-membrane autophagosomes that mediate bulk cytoplasmic and organelle degradation. Here we report the modification of single-membrane vacuoles in cells by autophagy proteins. Light Chain 3 (LC3), a component of autophagosomes, is recruited to single-membrane entotic vacuoles, macropinosomes, and phagosomes harboring apoptotic cells, in a manner dependent on lipidation machinery including Atg5 and Atg7, and the class III PI-3-kinase Vps34. These downstream components of autophagy machinery, but not the upstream mTor-regulated Ulk- Atg13-Fip200 complex, facilitate lysosome fusion to single membranes and the degradation of internalized cargo. For entosis, a live cell engulfment program, the autophagy protein-dependent fusion of lysosomes to vacuolar membranes leads to the death of internalized cells, which are killed by their hosts. As pathogen-containing phagosomes can be targeted in a similar manner, the death of epithelial cells by this mechanism mimics pathogen destruction. These data define the targeting of single-membrane vacuoles as a property of autophagy pathway proteins in cells in the absence of pathogenic organisms.
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影响因子：
56.9
作者：
Kawane, K;Fukuyama, H;Nagata, S
通讯作者：
Nagata, S
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
3.3
作者：
Jung, Chang Hwa;Jun, Chang Bong;Kim, Do-Hyung
通讯作者：
Kim, Do-Hyung
影响因子：
3.3
作者：
Cheong, H;Yorimitsu, T;Klionsky, DJ
通讯作者：
Klionsky, DJ