Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17.
Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17.
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DOI：
10.1038/ncomms15406
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发表时间：
2017-05-15
影响因子：
16.6
通讯作者：
Tagaya M
中科院分区：
文献类型：
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作者：
Arasaki K;Mikami Y;Shames SR;Inoue H;Wakana Y;Tagaya M
在巨噬细胞感染过程中，嗜肺军团菌分泌效应蛋白，诱导质膜衍生的液泡转化为内质网（ER）样的复制液泡。这些内质网样液泡最终与内质网融合，病原体在这里复制。在这里，我们发现嗜肺乳杆菌效应物lp1137是一种丝氨酸蛋白酶，靶向线粒体及其相关膜。Lpg1137结合并切割syntaxin 17， syntaxin 17是一种可溶性n -乙基马酰亚胺敏感因子附着蛋白受体（SNARE）蛋白，已知在喂食细胞中通过与线粒体裂变因子Drp1相互作用参与线粒体动力学调节，在饥饿细胞中通过与Atg14L和其他SNARE相互作用参与自噬。syntaxin 17的断裂不仅抑制自噬，还抑制staurosporine诱导的细胞凋亡，这种凋亡以Bax、drp1依赖的方式发生。因此，嗜肺乳杆菌可以通过切割syntaxin 17来关闭er -线粒体的通讯。致病菌嗜肺军团菌在巨噬细胞内复制。在这里，作者发现嗜肺乳杆菌分泌一种效应蛋白，可以切割宿主蛋白syntaxin 17，从而抑制宿主细胞的自噬和staurosporine诱导的细胞凋亡。
During infection of macrophages, the pathogenic bacterium Legionella pneumophila secretes effector proteins that induce the conversion of the plasma membrane-derived vacuole into an endoplasmic reticulum (ER)-like replicative vacuole. These ER-like vacuoles are ultimately fused with the ER, where the pathogen replicates. Here we show that the L. pneumophila effector Lpg1137 is a serine protease that targets the mitochondria and their associated membranes. Lpg1137 binds to and cleaves syntaxin 17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that is known to participate in the regulation of mitochondrial dynamics through interaction with the mitochondrial fission factor Drp1 in fed cells and in autophagy through interaction with Atg14L and other SNAREs in starved cells. Cleavage of syntaxin 17 inhibits not only autophagy but also staurosporine-induced apoptosis occurring in a Bax, Drp1-dependent manner. Thus, L. pneumophila can shut down ER–mitochondria communication through cleavage of syntaxin 17. The pathogenic bacterium Legionella pneumophila replicates within macrophages. Here, the authors show that L. pneumophila secretes an effector protein that cleaves the host protein syntaxin 17, thus inhibiting autophagy and staurosporine-induced apoptosis in the host cell.