RT Journal Article
SR Electronic
T1 Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 757013
DO 10.1101/757013
A1 Lauren Penfield
A1 Raakhee Shankar
A1 Erik Szentgyörgyi
A1 Alyssa Laffitte
A1 Michael Mauro
A1 Anjon Audhya
A1 Thomas Müller-Reichert
A1 Shirin Bahmanyar
YR 2019
UL http://biorxiv.org/content/early/2019/09/04/757013.abstract
AB The nuclear permeability barrier depends on closure of holes in the nuclear envelope (NE). Here, we use meiotic C. elegans oocytes to demonstrate that local control of glycerophospholipid synthesis by CNEP-1/CTDNEP1 regulates the insertion of ER sheets into NE holes and functions independently of ESCRT-III to ensure NE closure. Deletion of CNEP-1 causes excess incorporation of ER membranes into NE holes and a defective NE permeability barrier. ESCRT-III components accumulate at the NE opening surrounding the meiotic spindle, and loss of NE adaptors for ESCRT-III exacerbates NE sealing defects in cnep-1 mutants. Limiting ER sheet production by restoring glycerophospholipid synthesis in cnep-1 mutants rescued NE permeability defects. 3D analysis showed that membrane sheets feed into and narrow NE holes occluded by meiotic spindle microtubules supporting a role for ER sheet insertion in NE closure. Thus, feeding of ER sheets into NE holes must be coordinated with production of ER sheets near the NE to promote NE closure.