Abstract
Amongst other cellular functions, the Endosomal Sorting Complex Required for Transport-III (ESCRT-III) machinery controls nuclear envelope (NE) reformation during mitotic exit by sealing holes in the reforming NE. ESCRT-III also acts to repair this organelle upon migration-induced rupture. The ESCRT-III component CHMP7 is responsible for recruitment of ESCRT-III to the NE. Here, we show that the N-terminus of CHMP7, comprising tandem Winged Helix (WH)-domains, is a membrane-binding module. This activity 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. Point mutations that disrupt membrane-binding prevent CHMP7 localising to the ER and its subsequent enrichment at the reforming NE. These mutations prevent both 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.
One Sentence Summary CHMP7’s atypical N-terminus is a membrane-binding module that allows assembly and function of ESCRT-III at the nuclear envelope during mitotic exit.
