Thaller, D.J., Tong, D., Marklew, C.J. et al. (6 more authors) (2021) Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations. Journal of Cell Biology, 220 (3). e202004222. ISSN 0021-9525
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Thaller et al. 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/) |
Keywords: | Membrane and lipid biology; Organelles |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/M027821/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Oct 2021 16:11 |
Last Modified: | 12 Oct 2021 16:11 |
Status: | Published |
Publisher: | Rockefeller University Press |
Refereed: | Yes |
Identification Number: | 10.1083/jcb.202004222 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178960 |
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Licence: CC-BY-NC-SA 4.0