CC2D1B coordinates ESCRT-III activity during the mitotic reformation of the nuclear envelope
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2018
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Elsevier
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Ventimiglia LN, Cuesta-Geijo MA, Martinelli N, Caballe A, Macheboeuf P, Miguet N, et al. CC2D1B Coordinates ESCRT-III Activity during the Mitotic Reformation of the Nuclear Envelope. Developmental Cell. 2018;47(5):547-563.e6.
Abstract
The coordinated reformation of the nuclear envelope (NE) after mitosis re-establishes the structural integrity and the functionality of the nuclear compartment. The endosomal sorting complex required for transport (ESCRT) machinery, a membrane remodeling pathway that is highly conserved in eukaryotes, has been recently involved in NE resealing by mediating the annular fusion of the nuclear membrane (NM). We show here that CC2D1B, a regulator of ESCRT polymerization, is required to re-establish the nuclear compartmentalization by coordinating endoplasmic reticulum (ER) membrane deposition around chromatin disks with ESCRT-III recruitment to the reforming NE. Accordingly, CC2D1B determines the spatiotemporal distribution of the CHMP7-ESCRT-III axis during NE reformation. Crucially, in CC2D1B-depleted cells, ESCRT activity is uncoupled from Spastin-mediated severing of spindle microtubules, resulting in persisting microtubules that compromise nuclear morphology. Therefore, we reveal CC2D1B as an essential regulatory factor that licenses the formation of ESCRT-III polymers to ensure the orderly reformation of the NE.
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Grants and funding:
WT102871MA
NIHR Comprehensive BRC
PhD fellowship from the Région Rhône-Alpes (Cluster 10 infectiologie)
Wellcome Trust Research Career Development Fellowship (093603/Z/10/Z)