Membrane Binding by CHMP7 Coordinates ESCRT-III-Dependent Nuclear Envelope Reformation.
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. While NE localization 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 ER, an organelle continuous with the NE, and it 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 modeling and structure-function analysis, we identify point mutations that disrupt membrane binding and prevent both ER localization 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 compartmentalization. These data identify a novel membrane-binding activity within an ESCRT-III subunit that is essential for post-mitotic nuclear regeneration.
Division of Cancer Studies, King's College London, London SE1 1UL, UK.
Yolanda
Y
Olmos
Division of Cancer Studies, King's College London, London SE1 1UL, UK.
Anna
A
Perdrix-Rosell
Division of Cancer Studies, King's College London, London SE1 1UL, UK. Electronic address: jeremy.carlton@kcl.ac.uk.
Jeremy G
JG
Carlton
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002455:Cell Division; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism*; D016415:Sequence Alignment
C514910:CHMP7 protein, human; D056827:Endosomal Sorting Complexes Required for Transport
ESCRT-III; cell biology; cell division; mitosis; nuclear envelope