An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system
An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system
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DOI：
10.7554/elife.45284
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发表时间：
2019-04-03
期刊：
影响因子：
7.7
通讯作者：
Lusk, C. Patrick
中科院分区：
文献类型：
--
作者：
Thaller, David J.;Allegretti, Matteo;Lusk, C. Patrick
与核孔复合物（NPC）选择性屏障耦合的核膜的完整性对于核质和细胞质的分离至关重要。机械膜破坏或对 NPC 组装的扰动会触发依赖于 ESCRT 的监视系统来密封核孔：如何感知和密封这些孔尚不清楚。使用出芽酵母模型，我们表明 ESCRT Chm7 和整合内核膜 (INM) 蛋白 Heh1 通过核转运在空间上分离，其中 Chm7 由 Xpo1/Crm1 主动输出。因此，INM 的暴露会触发 Heh1 局部激活 Chm7 的监视。 Chm7 过度激活的位点显示 INM 处有窗状片，并且核膜突出位点处有潜在的膜传递。我们的数据表明，对核膜屏障的扰动将导致局部核膜重塑，以促进膜密封。我们的研究结果对与 NPC 组装和核膜完整性相关的疾病机制具有影响。
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.