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Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2166-E2175. doi: 10.1073/pnas.1613916114. Epub 2017 Feb 27.

LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.

Author information

1
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112.
2
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158.
3
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112.
4
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
5
Health Sciences Center (HSC) Imaging Core Facility, University of Utah, Salt Lake City, UT 84122.
6
HSC Electron Microscopy Core Facility, University of Utah, Salt Lake City, UT 84122.
7
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112; adam.frost@ucsf.edu wes@biochem.utah.edu katharine.ullman@hci.utah.edu.
8
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112; adam.frost@ucsf.edu wes@biochem.utah.edu katharine.ullman@hci.utah.edu.

Abstract

Endosomal sorting complexes required for transport III (ESCRT-III) proteins have been implicated in sealing the nuclear envelope in mammals, spindle pole body dynamics in fission yeast, and surveillance of defective nuclear pore complexes in budding yeast. Here, we report that Lem2p (LEM2), a member of the LEM (Lap2-Emerin-Man1) family of inner nuclear membrane proteins, and the ESCRT-II/ESCRT-III hybrid protein Cmp7p (CHMP7), work together to recruit additional ESCRT-III proteins to holes in the nuclear membrane. In Schizosaccharomyces pombe, deletion of the ATPase vps4 leads to severe defects in nuclear morphology and integrity. These phenotypes are suppressed by loss-of-function mutations that arise spontaneously in lem2 or cmp7, implying that these proteins may function upstream in the same pathway. Building on these genetic interactions, we explored the role of LEM2 during nuclear envelope reformation in human cells. We found that CHMP7 and LEM2 enrich at the same region of the chromatin disk periphery during this window of cell division and that CHMP7 can bind directly to the C-terminal domain of LEM2 in vitro. We further found that, during nuclear envelope formation, recruitment of the ESCRT factors CHMP7, CHMP2A, and IST1/CHMP8 all depend on LEM2 in human cells. We conclude that Lem2p/LEM2 is a conserved nuclear site-specific adaptor that recruits Cmp7p/CHMP7 and downstream ESCRT factors to the nuclear envelope.

KEYWORDS:

CHMP7; ESCRT-III; LEM2; VPS4; nuclear envelope

PMID:
28242692
PMCID:
PMC5358359
DOI:
10.1073/pnas.1613916114
[Indexed for MEDLINE]
Free PMC Article

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