在动物细胞分裂的早期阶段，核被膜破裂，而一旦细胞分裂在“后期”(anaphase)结束，核被膜则必须在两个子细胞的细胞核周围重新形成。我们知道，核被膜是从被称为“内质网”的另一个细胞器的膜形成的，而且它是通过一个膜融合步骤被封闭起来的，但我们对融合机制仍然只是部分了解。两个小组在本期Nature上报告说，这一过程是由ESCRT-III调控的，它是一种蛋白复合物，以在各种细胞过程中的膜收缩和封闭功能最为人们所知。Harald Stenmark及同事发现，ESCRT-III与另外两种蛋白VPS4和spastin在一个与“胞质分裂”机制相似的过程中共同协调被膜融合和纺锤体分解，以确保两个子细胞的物理分离。Jeremy Carlton及同事发现，ESCRT-III的CHMP2A成分被引导到正在形成中的核被膜上，在那里它通过与CHMP4B结合、并在UFD1 (以前被发现与核被膜融合相关的p97复合物的一个成分)的帮助下定位到融合点上。

    原文链接：Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing

    At the onset of metazoan cell division the nuclear envelope breaks down to enable capture of chromosomes by the microtubule-containing spindle apparatus1. During anaphase, when chromosomes have separated, the nuclear envelope is reassembled around the forming daughter nuclei. How the nuclear envelope is sealed, and how this is coordinated with spindle disassembly, is largely unknown. Here we show that endosomal sorting complex required for transport (ESCRT)-III, previously found to promote membrane constriction and sealing during receptor sorting, virus budding, cytokinesis and plasma membrane repair, is transiently recruited to the reassembling nuclear envelope during late anaphase. ESCRT-III and its regulatory AAA (ATPase associated with diverse cellular activities) ATPase VPS4 are specifically recruited by the ESCRT-III-like protein CHMP7 to sites wher the reforming nuclear envelope engulfs spindle microtubules. Subsequent association of another ESCRT-III-like protein, IST1, directly recruits the AAA ATPase spastin to sever microtubules. Disrupting spastin function impairs spindle disassembly and results in extended localization of ESCRT-III at the nuclear envelope. Interference with ESCRT-III functions in anaphase is accompanied by delayed microtubule disassembly, compromised nuclear integrity and the appearance of DNA damage foci in subsequent interphase. We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly at nuclear envelope–microtubule intersection sites during mitotic exit to ensure nuclear integrity and genome safeguarding, with a striking mechanistic parallel to cytokinetic abscission.

    ESCRT-III controls nuclear envelope reformation

    During telophase, the nuclear envelope (NE) reforms around daughter nuclei to ensure proper segregation of nuclear and cytoplasmic contents. NE reformation requires the coating of chromatin by membrane derived from the endoplasmic reticulum, and a subsequent annular fusion step to ensure that the formed envelope is sealed. How annular fusion is accomplished is unknown, but it is thought to involve the p97 AAA-ATPase complex and bears a topological equivalence to the membrane fusion event that occurs during the abscission phase of cytokinesis. Here we show that the endosomal sorting complex required for transport-III (ESCRT-III) machinery localizes to sites of annular fusion in the forming NE in human cells, and is necessary for proper post-mitotic nucleo-cytoplasmic compartmentalization. The ESCRT-III component charged multivesicular body protein 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides an activity essential for NE reformation. Localization also requires the p97 complex member ubiquitin fusion and degradation 1 (UFD1). Our results describe a novel role for the ESCRT machinery in cell division and demonstrate a conservation of the machineries involved in topologically equivalent mitotic membrane remodelling events.