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ESCRT-III controls nuclear envelope reformation

2015; Nature Portfolio; Volume: 522; Issue: 7555 Linguagem: Inglês

10.1038/nature14503

1476-4687

Yolanda Olmos, Lorna Hodgson, Judith Mantell, Paul Verkade, Jeremy G. Carlton,

Microtubule and mitosis dynamics

The ESCRT-III complex is implicated in the reformation of the nuclear envelope; the CHMP2A component of ESCRT-III is directed to the forming nuclear envelope through classical ESCRT-assembly mechanisms, with the help of the p97 complex component UFD1, and provides an activity essential for nuclear envelope reformation. At an early stage of cell division in animal cells the nuclear envelope breaks down, and once cell division draws to a close at anaphase, the envelope must reform around the nuclei of the two daughter cells. It is known that the nuclear envelope is derived from the membranes of another organelle, the endoplasmic reticulum, and that it is sealed through a membrane fusion step, but the mechanism of fusion remains partially understood. Two groups report this week [in this issue of Nature] that this process is regulated by ESCRT-III, a protein complex best known for membrane constriction and sealing during various cellular processes. Harald Stenmark and colleagues show that ESCRT-III and two other proteins, VPS4 and spastin, cooperatively coordinate envelope fusion and spindle disassembly in a process mechanistically similar to the cytokinesis that ensures physical separation of the two daughter cells. Jeremy Carlton and colleagues find that the CHMP2A component of ESCRT-III is directed to the forming nuclear envelope where it localizes to sites of fusion through binding to CHMP4B, and with the help of UFD1 — a component of the p97 complex previously implicated in nuclear envelope fusion. During telophase, the nuclear envelope (NE) reforms around daughter nuclei to ensure proper segregation of nuclear and cytoplasmic contents1,2,3,4. 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 sealed1,2,4,5. 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 cytokinesis1,6. 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.