CC2D1B Coordinates ESCRT-III Activity during the Mitotic Reformation of the Nuclear Envelope

TY - JOUR

T1 - CC2D1B Coordinates ESCRT-III Activity during the Mitotic Reformation of the Nuclear Envelope

AU - Ventimiglia, Leandro N.

AU - Cuesta-Geijo, Miguel Angel

AU - Martinelli, Nicolas

AU - Caballe, Anna

AU - Macheboeuf, Pauline

AU - Miguet, Nolwenn

AU - Parnham, Ian M.

AU - Olmos, Yolanda

AU - Carlton, Jeremy G.

AU - Weissenhorn, Winfried

AU - Martin-Serrano, Juan

PY - 2018/12/3

Y1 - 2018/12/3

N2 - © 2018 The Author(s) 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. A faithful reformation of the nuclear envelope after mitosis is critical to ensure the proper compartmentalization of the genetic material. Ventimiglia et al. identified CC2D1B as a key regulator of this process to ensure properly timed ESCRT-III machinery recruitment and licensing of ESCRT-III filaments for nuclear envelope resealing.

AB - © 2018 The Author(s) 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. A faithful reformation of the nuclear envelope after mitosis is critical to ensure the proper compartmentalization of the genetic material. Ventimiglia et al. identified CC2D1B as a key regulator of this process to ensure properly timed ESCRT-III machinery recruitment and licensing of ESCRT-III filaments for nuclear envelope resealing.

KW - ESCRT

KW - microtubules

KW - nuclear envelope

KW - Spastin

UR - https://www.scopus.com/pages/publications/85056704297

U2 - 10.1016/j.devcel.2018.11.012

DO - 10.1016/j.devcel.2018.11.012

M3 - Article

C2 - 30513301

AN - SCOPUS:85056704297

SN - 1534-5807

VL - 47

SP - 547-563.e6

JO - Developmental Cell

JF - Developmental Cell

IS - 5

ER -