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

Lauren Penfield, Raakhee Shankar, Erik Szentgyörgyi, Alyssa Laffitte, Michael Mauro, Anjon Audhya, Thomas Müller-Reichert, Shirin Bahmanyar
doi: https://doi.org/10.1101/757013
Lauren Penfield
Department of Molecular, Cellular and Developmental Biology, New Haven, CT 06511
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Raakhee Shankar
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin
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Erik Szentgyörgyi
Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Alyssa Laffitte
Department of Molecular, Cellular and Developmental Biology, New Haven, CT 06511
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Michael Mauro
Department of Molecular, Cellular and Developmental Biology, New Haven, CT 06511
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Anjon Audhya
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin
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Thomas Müller-Reichert
Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Shirin Bahmanyar
Department of Molecular, Cellular and Developmental Biology, New Haven, CT 06511
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  • For correspondence: shirin.bahmanyar@yale.edu
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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.

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Posted September 04, 2019.
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Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure
Lauren Penfield, Raakhee Shankar, Erik Szentgyörgyi, Alyssa Laffitte, Michael Mauro, Anjon Audhya, Thomas Müller-Reichert, Shirin Bahmanyar
bioRxiv 757013; doi: https://doi.org/10.1101/757013
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Local regulation of lipid synthesis controls ER sheet insertion into nuclear envelope holes to complete nuclear closure
Lauren Penfield, Raakhee Shankar, Erik Szentgyörgyi, Alyssa Laffitte, Michael Mauro, Anjon Audhya, Thomas Müller-Reichert, Shirin Bahmanyar
bioRxiv 757013; doi: https://doi.org/10.1101/757013

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