RRC ID 48803
著者 Gu M, LaJoie D, Chen OS, von Appen A, Ladinsky MS, Redd MJ, Nikolova L, Bjorkman PJ, Sundquist WI, Ullman KS, Frost A.
タイトル LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 114(11)
ページ E2166-E2175
公開日 2017-3-14
DOI 10.1073/pnas.1613916114
PII 1613916114
PMID 28242692
PMC PMC5358359
MeSH Alleles Endosomal Sorting Complexes Required for Transport / genetics Endosomal Sorting Complexes Required for Transport / metabolism* HeLa Cells Humans Membrane Proteins / genetics Membrane Proteins / metabolism* Microscopy, Fluorescence Mitosis / genetics Models, Biological Nuclear Envelope / metabolism* Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phenotype Protein Binding Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces / ultrastructure Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Sequence Deletion Time-Lapse Imaging
IF 9.412
引用数 45
WOS 分野 CELL BIOLOGY
リソース情報
遺伝子材料 pDUAL (RDB06178)