Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry
Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry
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DOI：
10.1038/s41467-020-14967-w
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发表时间：
2020-02-28
影响因子：
16.6
通讯作者：
Tsai, Billy
中科院分区：
文献类型：
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作者：
Bagchi, Parikshit;Torres, Mauricio;Tsai, Billy
虽然病毒必须通过复杂的宿主内膜系统感染细胞，但实现这一目标的策略尚不清楚。在进入过程中，多瘤病毒SV 40从晚期核内体（LE）分选到内质网（ER）以引起感染，但这是如何实现的仍然是个谜。在这里，我们发现EMC4和EMC7，两个ER膜蛋白复合物（EMC）亚基，通过促进病毒的LE到ER靶向来支持SV40感染。它们通过与LE相关的Rab7结合来实现这一点，大概是为了稳定LE和ER之间的接触。这些EMC亚单位也结合到ER驻留融合机器组件syntaxin18，这是SV40到达ER所必需的。我们的数据表明，EMC4和EMC7作为分子系链，将两个细胞内区室相互连接，使病毒能够在这些区室之间有效运输。由于LE到ER运输的细胞货物是不清楚的，我们的研究结果具有广泛的意义，照亮细胞器间的货物运输。
Although viruses must navigate the complex host endomembrane system to infect cells, the strategies used to achieve this is unclear. During entry, polyomavirus SV40 is sorted from the late endosome (LE) to the endoplasmic reticulum (ER) to cause infection, yet how this is accomplished remains enigmatic. Here we find that EMC4 and EMC7, two ER membrane protein complex (EMC) subunits, support SV40 infection by promoting LE-to-ER targeting of the virus. They do this by engaging LE-associated Rab7, presumably to stabilize contact between the LE and ER. These EMC subunits also bind to the ER-resident fusion machinery component syntaxin18, which is required for SV40-arrival to the ER. Our data suggest that EMC4 and EMC7 act as molecular tethers, inter-connecting two intracellular compartments to enable efficient transport of a virus between these compartments. As LE-to-ER transport of cellular cargos is unclear, our results have broad implications for illuminating inter-organelle cargo transport.