Membrane binding by CHMP7 coordinates ESCRT-III dependent nuclear envelope reformation

TY - JOUR

T1 - Membrane binding by CHMP7 coordinates ESCRT-III dependent nuclear envelope reformation

AU - Olmos, Yolanda

AU - Perdrix Rosell, Anna

AU - Carlton, Jeremy Graham

PY - 2016/10/10

Y1 - 2016/10/10

N2 - In addition to its role in membrane abscission during cytokinesis, viral budding, endosomal sorting and plasma membrane repair [1], the Endosomal Sorting Complex Required for Transport-III (ESCRT-III) machinery has recently been shown to seal holes in the reforming nuclear envelope (NE) during mitotic exit [2,3]. ESCRT-III also acts during interphase to repair the NE upon migration-induced rupture [4,5], highlighting its key role as an orchestrator of membrane integrity at this organelle. Whilst NE localisation of ESCRT-III is dependent upon the ESCRT-III component CHMP7 [3], it is unclear how this complex is able to engage nuclear membranes. Here, we show that the N-terminus of CHMP7 acts as a novel membrane-binding module. This membrane-binding ability allows CHMP7 to bind to the Endoplasmic Reticulum (ER), an organelle continuous with the NE, and provides a platform to direct NE-recruitment of ESCRT-III during mitotic exit. CHMP7’s N-terminus comprises tandem Winged-Helix domains [6] and by using homology modelling and structure-function analysis, we identify point mutations that disrupt membrane-binding and prevent both ER-localisation of CHMP7 and its subsequent enrichment at the reforming NE. These mutations also prevent assembly of downstream ESCRT-III components at the reforming NE and proper establishment of post-mitotic nucleo-cytoplasmic compartmentalisation. These data identify a novel membrane-binding activity within an ESCRT-III subunit that is essential for post-mitotic nuclear regeneration.

AB - In addition to its role in membrane abscission during cytokinesis, viral budding, endosomal sorting and plasma membrane repair [1], the Endosomal Sorting Complex Required for Transport-III (ESCRT-III) machinery has recently been shown to seal holes in the reforming nuclear envelope (NE) during mitotic exit [2,3]. ESCRT-III also acts during interphase to repair the NE upon migration-induced rupture [4,5], highlighting its key role as an orchestrator of membrane integrity at this organelle. Whilst NE localisation of ESCRT-III is dependent upon the ESCRT-III component CHMP7 [3], it is unclear how this complex is able to engage nuclear membranes. Here, we show that the N-terminus of CHMP7 acts as a novel membrane-binding module. This membrane-binding ability allows CHMP7 to bind to the Endoplasmic Reticulum (ER), an organelle continuous with the NE, and provides a platform to direct NE-recruitment of ESCRT-III during mitotic exit. CHMP7’s N-terminus comprises tandem Winged-Helix domains [6] and by using homology modelling and structure-function analysis, we identify point mutations that disrupt membrane-binding and prevent both ER-localisation of CHMP7 and its subsequent enrichment at the reforming NE. These mutations also prevent assembly of downstream ESCRT-III components at the reforming NE and proper establishment of post-mitotic nucleo-cytoplasmic compartmentalisation. These data identify a novel membrane-binding activity within an ESCRT-III subunit that is essential for post-mitotic nuclear regeneration.

KW - Cell Biology

KW - ESCRT

KW - Nuclear Envelope

U2 - 10.1016/j.cub.2016.07.039

DO - 10.1016/j.cub.2016.07.039

M3 - Article

SN - 0960-9822

VL - 26

SP - 2635

EP - 2641

JO - Current Biology

JF - Current Biology

IS - 19

ER -