scholarly journals Evolvement of LEM proteins as chromatin tethers at the nuclear periphery

2011 ◽  
Vol 39 (6) ◽  
pp. 1735-1741 ◽  
Author(s):  
Andreas Brachner ◽  
Roland Foisner
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Transmembrane Proteins ◽  
Signal Transducer ◽  
Protein Inhibitor ◽  
Inner Nuclear Membrane ◽  
Unicellular Eukaryotes ◽  
Attachment Factor ◽  
Affect Gene Expression

The nuclear envelope in eukaryotic cells has important roles in chromatin organization. The inner nuclear membrane contains over 60 transmembrane proteins. LEM [LAP2 (lamina-associated polypeptide 2)/emerin/MAN1] domain-containing proteins of the inner nuclear membrane are involved in tethering chromatin to the nuclear envelope and affect gene expression. They contain a common structural, bihelical motif, the so-called LEM domain, which mediates binding to a conserved chromatin protein, BAF (barrier to autointegration factor). Interestingly, this domain is highly related to other bihelical motifs, termed HeH (helix–extension–helix) and SAP {SAF (scaffold attachment factor)/acinus/PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)]} motifs, which are directly linked to DNA. In the present paper, we summarize evidence that the LEM motif evolved from the HeH and SAP domains concomitantly with BAF. In addition, we discuss the potential evolution of HeH/SAP and LEM domain-containing proteins and their role in chromatin tethering and gene regulation from unicellular eukaryotes to mammals.

scholarly journals Lamin-dependent Localization of UNC-84, A Protein Required for Nuclear Migration in Caenorhabditis elegans

2002 ◽  
Vol 13 (3) ◽  
pp. 892-901 ◽  
Author(s):  
Kenneth K. Lee ◽  
Daniel Starr ◽  
Merav Cohen ◽  
Jun Liu ◽  
Min Han ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Nuclear Migration ◽  
Cell Stage ◽  
Inner Nuclear Membrane ◽  
Late Anaphase

Mutations in the Caenorhabditis elegans unc-84 gene cause defects in nuclear migration and anchoring. We show that endogenous UNC-84 protein colocalizes with Ce-lamin at the nuclear envelope and that the envelope localization of UNC-84 requires Ce-lamin. We also show that during mitosis, UNC-84 remains at the nuclear periphery until late anaphase, similar to known inner nuclear membrane proteins. UNC-84 protein is first detected at the 26-cell stage and thereafter is present in most cells during development and in adults. UNC-84 is properly expressed in unc-83 andanc-1 lines, which have phenotypes similar tounc-84, suggesting that neither the expression nor nuclear envelope localization of UNC-84 depends on UNC-83 or ANC-1 proteins. The envelope localization of Ce-lamin, Ce-emerin, Ce-MAN1, and nucleoporins are unaffected by the loss of UNC-84. UNC-84 is not required for centrosome attachment to the nucleus because centrosomes are localized normally in unc-84 hyp7 cells despite a nuclear migration defect. Models for UNC-84 localization are discussed.

scholarly journals Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

2018 ◽  
Author(s):  
Li-Chun Cheng ◽  
Sabyasachi Baboo ◽  
Cory Lindsay ◽  
Liza Brusman ◽  
Salvador Martinez-Bartolomé ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Transmembrane Proteins ◽  
Nuclear Lamina ◽  
Cell Types ◽  
Nucleocytoplasmic Transport ◽  
Membrane Dynamics ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes

AbstractThe nuclear envelope (NE) is an endoplasmic reticulum (ER) subdomain that contains characteristic components dedicated to nuclear functions. These include nuclear pore complexes (NPCs) – the channels for nucleocytoplasmic transport, and the nuclear lamina (NL) – a scaffold for NE and chromatin organization at the nuclear periphery. Since numerous human diseases associated with NE/NL proteins occur in mesenchyme-derived cells, a more comprehensive characterization of proteins concentrated at the NE in these cell types is warranted. Accordingly, we used proteomics to analyze NE and other subcellular fractions isolated from mesenchymal stem cells and from differentiated adipocytes and myocytes. We evaluated the proteomics datasets to calculate relative protein enrichment in the NE fraction, using a spectral abundance-based scoring system that accurately described most benchmark proteins. We then examined five high-scoring transmembrane proteins expressed in all three cell types that were not previously known to be enriched at the NE. Using quantitative immunofluorescence microscopy to track ectopically expressed proteins, we validated that all five of these components are substantially concentrated at the NE of multiple cell types. One (Itprip) is exposed to the outer nuclear membrane, a second (Smpd4) is enriched at the NPC, and the three others (Mfsd10, Tmx4, and Arl6ip6) are suggested to reside in the inner nuclear membrane. Considering their sequences and other features, these proteins provide new focal points for studying the functions and membrane dynamics of the NE. Our datasets should be useful for identifying additional NE-concentrated proteins, and for evaluating candidates that are identified in screening.

scholarly journals Unrestrained ESCRT-III drives chromosome fragmentation and micronuclear catastrophe

2019 ◽  
Author(s):  
Marina Vietri ◽  
Sebastian W. Schultz ◽  
Aurélie Bellanger ◽  
Carl M. Jones ◽  
Camilla Raiborg ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Genome Stability ◽  
Membrane Deformation ◽  
Chromosome Fragmentation ◽  
Inner Nuclear Membrane ◽  
Membrane Rupture ◽  
Membrane Fission ◽  
Stable Association ◽  
Inner Nuclear Membrane Protein

AbstractThe ESCRT-III membrane fission machinery1,2 restores nuclear envelope integrity during mitotic exit3,4 and interphase5,6. Whereas primary nuclei resealing takes minutes, micronuclear envelope ruptures appear irreversible and result in catastrophic collapse associated with chromosome fragmentation and rearrangements (chromothripsis), thought to be a major driving force in cancer development7-10. Despite its importance11-13, the mechanistic underpinnings of nuclear envelope sealing in primary nuclei and the defects observed in micronuclei remain largely unknown. Here we show that CHMP7, the nucleator of ESCRT-III filaments at the nuclear envelope3,14, and the inner nuclear membrane protein LEMD215 act as a compartmentalization sensor detecting the loss of nuclear integrity. In cells with intact nuclear envelope, CHMP7 is actively excluded from the nucleus to preclude its binding to LEMD2. Nuclear influx of CHMP7 results in stable association with LEMD2 at the inner nuclear membrane that licenses local polymerization of ESCRT-III. Tight control of nuclear CHMP7 levels is critical, as induction of nuclear CHMP7 mutants is sufficient to induce unrestrained growth of ESCRT-III foci at the nuclear envelope, causing dramatic membrane deformation, local DNA torsional stress, single-stranded DNA formation and fragmentation of the underlying chromosomes. At micronuclei, membrane rupture is not associated with repair despite timely recruitment of ESCRT-III. Instead, micronuclei inherently lack the capacity to restrict accumulation of CHMP7 and LEMD2. This drives unrestrained ESCRT-III recruitment, membrane deformation and DNA defects that strikingly resemble those at primary nuclei upon induction of nuclear CHMP7 mutants. Preventing ESCRT-III recruitment suppresses membrane deformation and DNA damage, without restoring nucleocytoplasmic compartmentalization. We propose that the ESCRT-III nuclear integrity surveillance machinery is a double-edged sword, as its exquisite sensitivity ensures rapid repair at primary nuclei while causing unrestrained polymerization at micronuclei, with catastrophic consequences for genome stability16-18.

scholarly journals BAF facilitates interphase nuclear membrane repair through recruitment of nuclear transmembrane proteins

2020 ◽  
Vol 31 (15) ◽  
pp. 1551-1560 ◽  
Author(s):  
Alexandra M. Young ◽  
Amanda L. Gunn ◽  
Emily M. Hatch
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Transmembrane Proteins ◽  
Membrane Repair ◽  
Membrane Rupture ◽  
Protein Barrier

Nuclear membrane rupture occurs during interphase in a variety of cell contexts, but how the membrane repairs remains poorly understood. Here we show that the nuclear envelope (NE) protein barrier-to-autointegration factor facilitates membrane repair by recruiting transmembrane NE proteins to rupture sites.

Function and assembly of nuclear pore complex proteins

1999 ◽  
Vol 77 (4) ◽  
pp. 321-329 ◽  
Author(s):  
Khaldon Bodoor ◽  
Sarah Shaikh ◽  
Paul Enarson ◽  
Sharmin Chowdhury ◽  
Davide Salina ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Nuclear Membrane ◽  
Current View ◽  
Nuclear Pore ◽  
Dynamic Component ◽  
Inner Nuclear Membrane ◽  
Inner Nuclear Membrane Protein ◽  
Nuclear Membrane Protein

Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between the nucleus and cytoplasm. The current view of NPC organization features a massive symmetrical framework that is embedded in the double membranes of the nuclear envelope. It embraces a central channel of as yet ill-defined structure but which may accommodate particles with diameters up to 26 nm provided that they bear specific import/export signals. Attached to both faces of the central framework are peripheral structures, short cytoplasmic filaments, and a nuclear basket assembly, which interact with molecules transiting the NPC. The mechanisms of assembly and the nature of NPC structural intermediates are still poorly understood. However, mutagenesis and expression studies have revealed discrete sequences within certain NPC proteins that are necessary and sufficient for their appropriate targeting. In addition, some details are emerging from observations on cells undergoing mitosis where the nuclear envelope is disassembled and its components, including NPC subunits, are dispersed throughout the mitotic cytoplasm. At the end of mitosis, all of these components are reutilized to form nuclear envelopes in the two daughter cells. To date, it has been possible to define a time course of postmitotic assembly for a group of NPC components (CAN/Nup214, Nup153, POM121, p62 and Tpr) relative to the integral inner nuclear membrane protein LAP2 and the NPC membrane glycoprotein gp210. Nup153, a dynamic component of the nuclear basket, associates with chromatin towards the end of anaphase coincident with, although independent of, the inner nuclear membrane protein, LAP2. Assembly of the remaining proteins follows that of the nuclear membranes and occurs in the sequence POM121, p62, CAN/Nup214 and gp210/Tpr. Since p62 remains as a complex with three other NPC proteins (p58, p54, p45) during mitosis, and CAN/Nup214 maintains a similar interaction with its partner, Nup84, the relative timing of assembly of these additional four proteins may also be inferred. These observations suggest that there is a sequential association of NPC proteins with chromosomes during nuclear envelope reformation and the recruitment of at least eight of these precedes that of gp210. These findings support a model in which it is POM121 rather than gp210 that defines initial membrane-associated NPC assembly intermediates and which may therefore represent an essential component of the central framework of the NPC. Key words: nuclear pore complex, nucleoporin, mitosis, nuclear transport

scholarly journals SUN-1 and ZYG-12, Mediators of Centrosome–Nucleus Attachment, Are a Functional SUN/KASH Pair in Caenorhabditis elegans

2009 ◽  
Vol 20 (21) ◽  
pp. 4586-4595 ◽  
Author(s):  
IL Minn ◽  
Melissa M. Rolls ◽  
Wendy Hanna-Rose ◽  
Christian J. Malone
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Coiled Coil ◽  
Physical Interaction ◽  
Type Ii ◽  
Inner Nuclear Membrane ◽  
Sequence Elements ◽  
Inner Nuclear Membrane Protein ◽  
Sun Domain

Klarsicht/ANC-1/Syne/homology (KASH)/Sad-1/UNC-84 (SUN) protein pairs can act as connectors between cytoplasmic organelles and the nucleoskeleton. Caenorhabditis elegans ZYG-12 and SUN-1 are essential for centrosome–nucleus attachment. Although SUN-1 has a canonical SUN domain, ZYG-12 has a divergent KASH domain. Here, we establish that the ZYG-12 mini KASH domain is functional and, in combination with a portion of coiled-coil domain, is sufficient for nuclear envelope localization. ZYG-12 and SUN-1 are hypothesized to be outer and inner nuclear membrane proteins, respectively, and to interact, but neither their topologies nor their physical interaction has been directly investigated. We show that ZYG-12 is a type II outer nuclear membrane (ONM) protein and that SUN-1 is a type II inner nuclear membrane protein. The proteins interact in the luminal space of the nuclear envelope via the ZYG-12 mini KASH domain and a region of SUN-1 that does not include the SUN domain. SUN-1 is hypothesized to restrict ZYG-12 to the ONM, preventing diffusion through the endoplasmic reticulum. We establish that ZYG-12 is indeed immobile at the ONM by using fluorescence recovery after photobleaching and show that SUN-1 is sufficient to localize ZYG-12 in cells. This work supports current models of KASH/SUN pairs and highlights the diversity in sequence elements defining KASH domains.

scholarly journals SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors

2015 ◽  
Vol 26 (10) ◽  
pp. 1918-1934 ◽  
Author(s):  
Sergio A. Mojica ◽  
Kelley M. Hovis ◽  
Matthew B. Frieman ◽  
Bao Tran ◽  
Ru-ching Hsia ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Lamina ◽  
Chlamydia Psittaci ◽  
Hek293 Cells ◽  
Secreted Protein ◽  
Inner Nuclear Membrane ◽  
Type Iii ◽  
Infected Cells ◽  
Digitonin Permeabilization

SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci–infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP–transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HEK293 cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence, including the nucleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membrane, suggesting that SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization, and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear “lamina” structure, or with a complex containing emerin was confirmed by GFP pull down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci.

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