title: ESCRT-III controls nuclear envelope reformation.
abstract: 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.
authors.affiliation: Division of Cancer Studies, Section of Cell Biology and Imaging, King's College London, London SE1 1UL, UK.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Olmos
authors.affiliation: School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Hodgson
authors.affiliation: 1] School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK [2] Wolfson Bioimaging Facility, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Mantell
authors.affiliation: 1] School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK [2] Wolfson Bioimaging Facility, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK [3] School of Physiology &Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Verkade
authors.affiliation: Division of Cancer Studies, Section of Cell Biology and Imaging, King's College London, London SE1 1UL, UK.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Carlton
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008561:Membrane Fusion; D008938:Mitosis; D009685:Nuclear Envelope / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D013692:Telophase
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C507674:CHMP2A protein, human; D002843:Chromatin; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C491497:UFD1 protein, human