Mechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)–binding capacity in the nuclear envelope (NE)–specific ESCRT, Chm7, in budding yeast. Chm7’s interaction with PA-rich membranes is mediated through a conserved hydrophobic stretch of amino acids, which confers recruitment to the NE in a manner that is independent of but required for Chm7’s interaction with the LAP2-emerin-MAN1 (LEM) domain protein Heh1 (LEM2). Consistent with the functional importance of PA binding, mutation of this region abrogates recruitment of Chm7 to membranes and abolishes Chm7 function in the context of NE herniations that form during defective nuclear pore complex (NPC) biogenesis. In fact, we show that a PA sensor specifically accumulates within these NE herniations. We suggest that local control of PA metabolism is important for ensuring productive NE remodeling and that its dysregulation may contribute to pathologies associated with defective NPC assembly.
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1 March 2021
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January 19 2021
Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations
David J. Thaller
,
David J. Thaller
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Danqing Tong
,
Danqing Tong
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Christopher J. Marklew
,
Christopher J. Marklew
2
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Brook Hill, Sheffield, UK
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Nicholas R. Ader
,
Nicholas R. Ader
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Philip J. Mannino
,
Philip J. Mannino
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Sapan Borah
,
Sapan Borah
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Megan C. King
,
Megan C. King
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
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Barbara Ciani
,
Barbara Ciani
2
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Brook Hill, Sheffield, UK
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C. Patrick Lusk
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Correspondence to C. Patrick Lusk: patrick.lusk@yale.edu
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David J. Thaller
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Danqing Tong
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Christopher J. Marklew
2
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Brook Hill, Sheffield, UK
Nicholas R. Ader
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Philip J. Mannino
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Sapan Borah
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Megan C. King
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Barbara Ciani
2
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Brook Hill, Sheffield, UK
C. Patrick Lusk
1
Department of Cell Biology, Yale School of Medicine, New Haven, CT
Correspondence to C. Patrick Lusk: patrick.lusk@yale.edu
Received:
April 30 2020
Revision Received:
November 04 2020
Accepted:
December 11 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Engineering and Physical Sciences Research Council
(EP/M027821/1)
National Institutes of Health
(R01 GM105672)
© 2021 Thaller et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (3): e202004222.
Article history
Received:
April 30 2020
Revision Received:
November 04 2020
Accepted:
December 11 2020
Connected Content
Citation
David J. Thaller, Danqing Tong, Christopher J. Marklew, Nicholas R. Ader, Philip J. Mannino, Sapan Borah, Megan C. King, Barbara Ciani, C. Patrick Lusk; Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations. J Cell Biol 1 March 2021; 220 (3): e202004222. doi: https://doi.org/10.1083/jcb.202004222
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