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An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system

机译:ESCRT-LEM蛋白监视系统已准备就绪可以直接监视核包膜和核转运系统

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摘要

The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these pores are sensed and sealed is ill defined. Using a budding yeast model, we show that the ESCRT Chm7 and the integral inner nuclear membrane (INM) protein Heh1 are spatially segregated by nuclear transport, with Chm7 being actively exported by Xpo1/Crm1. Thus, the exposure of the INM triggers surveillance with Heh1 locally activating Chm7. Sites of Chm7 hyperactivation show fenestrated sheets at the INM and potential membrane delivery at sites of nuclear envelope herniation. Our data suggest that perturbation to the nuclear envelope barrier would lead to local nuclear membrane remodeling to promote membrane sealing. Our findings have implications for disease mechanisms linked to NPC assembly and nuclear envelope integrity.
机译:核膜的完整性与核孔复合物(NPC)的选择性屏障耦合对于核质和细胞质的分离至关重要。机械性膜破裂或对NPC组件的干扰触发了依赖ESCRT的监视系统,该系统密封了核孔:如何感知和密封这些孔的定义不明确。使用出芽的酵母模型,我们显示了ESCRT Chm7和完整的内核膜(INM)蛋白Heh1在空间上是通过核转运分离的,而Chm7被Xpo1 / Crm1主动输出。因此,INM的暴露触发了Heh1局部激活Chm7的监视。 Chm7过度活化的部位在INM处显示有窗孔的薄片,而在核包膜疝的部位则可能有膜传递。我们的数据表明,对核包膜屏障的干扰将导致局部核膜重塑,从而促进膜密封。我们的发现对与NPC组装和核包膜完整性有关的疾病机制具有影响。

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