Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure

Abstract

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.

Factors promoting nuclear envelope assembly independent of the canonical ESCRT pathway

“…In addition to dedicated membrane fusion machineries, such as ESCRT, membrane fusion can be enhanced by altering the biophysical properties of the lipid bilayer ( Chernomordik and Kozlov, 2003 ; Kinugasa et al, 2019 ; Penfield et al, 2019 ). Interestingly, our screen identified several mutations in ole1 , the gene encoding the only Δ9 fatty acid desaturase in S. japonicus ( Stukey et al, 1989 ; Makarova et al, 2020 ).…”