CDK1 controls CHMP7-dependent nuclear envelope reformation



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Gatta, Alberto T. and Olmos Buchelt, Yolanda and Stoten, Caroline L. and Chen, Qu and Rosenthal, Peter B. and Carlton, Jeremy G. (2021) CDK1 controls CHMP7-dependent nuclear envelope reformation. eLife, 10 (e599). pp. 1-25. ISSN 2050-084X

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Through membrane sealing and disassembly of spindle microtubules, the Endosomal Sorting Complex Required for Transport-III (ESCRT-III) machinery has emerged as a key player in the regeneration of a sealed nuclear envelope (NE) during mitotic exit, and in the repair of this organelle during interphase rupture. ESCRT-III assembly at the NE occurs transiently during mitotic (M) exit and is initiated when CHMP7, an ER-localised ESCRT-II/ESCRT-III hybrid protein, interacts with the Inner Nuclear Membrane (INM) protein LEM2. Whilst classical nucleocytoplasmic transport mechanisms have been proposed to separate LEM2 and CHMP7 during interphase, it is unclear how CHMP7 assembly is suppressed in mitosis when NE and ER identities are mixed. Here, we use live cell imaging and protein biochemistry to examine the biology of these proteins during M-exit. Firstly, we show that CHMP7 plays an important role in the dissolution of LEM2 clusters that form at the NE during M-exit. Secondly, we show that CDK1 phosphorylates CHMP7 upon M-entry at Ser3 and Ser441 and that this phosphorylation reduces CHMP7’s interaction with LEM2, limiting its assembly during M-phase. We show that spatiotemporal differences in the dephosphorylation of CHMP7 license its assembly at the NE during telophase, but restrict its assembly on the ER at this time. Without CDK1 phosphorylation, CHMP7 undergoes inappropriate assembly in the peripheral ER during M-exit, capturing LEM2 and downstream ESCRT-III components. Lastly, we establish that a microtubule network is dispensable for ESCRT-III assembly at the reforming nuclear envelope. These data identify a key cell-cycle control programme allowing ESCRT-III-dependent nuclear regeneration.

Item Type:Article
Uncontrolled Keywords:Wnt signalling; β-catenin; Thymic epithelial cells (TECs); Thymocytes
Subjects:Medical sciences > Biology > Cytology
Medical sciences > Biology > Biochemistry
ID Code:71617
Deposited On:04 Apr 2022 09:03
Last Modified:11 Oct 2022 11:40

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