Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown
- Shirin Bahmanyar1,5,7,
- Ronald Biggs1,
- Amber L. Schuh2,
- Arshad Desai1,
- Thomas Müller-Reichert3,
- Anjon Audhya2,
- Jack E. Dixon4 and
- Karen Oegema1,6,7
- 1Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA;
- 2Department of Biomolecular Chemistry, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706, USA;
- 3Medical Theoretical Center, Dresden University of Technology, 01307 Dresden, Germany;
- 4Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
Abstract
The nuclear envelope is a subdomain of the endoplasmic reticulum (ER). Here we characterize CNEP-1 (CTD [C-terminal domain] nuclear envelope phosphatase-1), a nuclear envelope-enriched activator of the ER-associated phosphatidic acid phosphatase lipin that promotes synthesis of major membrane phospholipids over phosphatidylinositol (PI). CNEP-1 inhibition led to ectopic ER sheets in the vicinity of the nucleus that encased the nuclear envelope and interfered with nuclear envelope breakdown (NEBD) during cell division. Reducing PI synthesis suppressed these phenotypes, indicating that CNEP-1 spatially regulates phospholipid flux, biasing it away from PI production in the vicinity of the nuclear envelope to prevent excess ER sheet formation and NEBD defects.
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Footnotes
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↵7 Corresponding authors
E-mail koegema{at}ucsd.edu
E-mail shirin.bahmanyar{at}yale.edu
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.230599.113.
- Received September 11, 2013.
- Accepted December 13, 2013.
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