Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nuclear Envelope”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1991

Transport across the nuclear envelope: enigmas and explanations.

The transport of molecules across the nuclear envelope plays a central role in the metabolism of the cell. Significant advances in three major areas highlight the limits of our current knowledge and point to the prospect of exciting future developments. Firstly, findings that ions and small proteins do not diffuse freely into the nucleus call into question the current views of nuclear envelope permeability. Secondly, indications that nuclear protein import can be regulated in conjunction with the cell cycle and development have been confirmed by the clear demonstration of regulated nuclear entry of specific transcription factors and morphogens. Thirdly, identification and characterisation of candidate receptor proteins indicates that the recognition of the nuclear targeting sequence occurs in the cytoplasm, suggesting that a different recognition event occurs at the nuclear pore.

Animals↗
PubMed2003

Calcium- and cell cycle-dependent association of annexin 11 with the nuclear envelope.

Annexin 11 is a widely expressed calcium- and phospholipid-binding protein that resides in the nucleoplasm in many cultured cell lines. This is in contrast to its most extensively characterized in vitro ligand, the small calcium-binding protein S100A6 (calcyclin), which is concentrated in the nuclear envelope. Here we have examined the significance of the association of annexin 11 and S100A6 by asking whether circumstances exist in which the two proteins occupy the same subcellular localization. First, we show that in both A431 and vascular smooth muscle cells, elevation of intracellular Ca2+ leads to translocation of annexin 11 from the nucleus to the nuclear envelope where it co-localizes with S100A6. We also demonstrate, using fusions of annexin 11 with green fluorescent protein, that whereas the C-terminal core domain of annexin 11 is essential for Ca2+ sensitivity, the N-terminal domain is required for targeting to the nuclear envelope. Second, we show that annexin 11 relocalizes to the nuclear envelope as A431 cells transit from early to mid-prophase. In late prophase, at the time of nuclear envelope breakdown, annexin 11 and S100A6 become intensely localized with lamina-associated polypeptide 2 to folds in the nuclear envelope. From metaphase to telophase S100A6 is degraded, but in late telophase annexin 11 associates with the reforming nuclear envelope before resuming a nucleoplasmic location in interphase. These results show that co-localization of annexin 11 and S100A6 at the nuclear envelope may be regulated either by elevation of intracellular Ca2+ or by cell cycle progression and provide the first evidence that these proteins may associate in vivo.

Annexins↗
PubMed1997

Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis.

We have analyzed the fate of several integral membrane proteins of the nuclear envelope during mitosis in cultured mammalian cells to determine whether nuclear membrane proteins are present in a vesicle population distinct from bulk ER membranes after mitotic nuclear envelope disassembly or are dispersed throughout the ER. Using immunofluorescence staining and confocal microscopy, we compared the localization of two inner nuclear membrane proteins (laminaassociated polypeptides 1 and 2 [LAP1 and LAP2]) and a nuclear pore membrane protein (gp210) to the distribution of bulk ER membranes, which was determined with lipid dyes (DiOC6 and R6) and polyclonal antibodies. We found that at the resolution of this technique, the three nuclear envelope markers become completely dispersed throughout ER membranes during mitosis. In agreement with these results, we detected LAP1 in most membranes containing ER markers by immunogold electron microscopy of metaphase cells. Together, these findings indicate that nuclear membranes lose their identity as a subcompartment of the ER during mitosis. We found that nuclear lamins begin to reassemble around chromosomes at the end of mitosis at the same time as LAP1 and LAP2 and propose that reassembly of the nuclear envelope at the end of mitosis involves sorting of integral membrane proteins to chromosome surfaces by binding interactions with lamins and chromatin.

3T3 Cells↗
PubMed1994

Use of dextran beads for live analysis of the nuclear division and nuclear envelope breakdown/reformation cycles in the Drosophila embryo.

We employ fluorescently labeled dextran beads to follow cycles of nuclear division and nuclear envelope breakdown in living Drosophila embryos. When injected into syncytial Drosophila embryos, 3000 mol wt fluorescently labeled dextran beads concentrate in the interphase nucleus. Through confocal microscopy, undisrupted multiple cycles of nuclear division are readily followed. In contrast, 40,000 mol wt fluorescently labeled dextran beads concentrate in the cytoplasm and enter the nucleus only after nuclear envelope breakdown during prophase. Once the nuclear envelope reforms during telophase, these large dextran beads are again excluded from the nuclei. The complementary behavior of the large and small dextran beads makes them applicable to a broad range of cellular studies. We employ the 40,000 mol wt fluorescein-labeled beads, in combination with rhodamine-labeled histones, to demonstrate that nuclear envelope breakdown occurs about 3.5-4.0 minutes prior to the initiation of anaphase.

Animals↗
PubMed2006

The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity.

Primate lentiviruses such as human immunodeficiency type 1 (HIV-1) have the capacity to infect non-dividing cells such as tissue macrophages. In the process, viral complementary DNA traverses the nuclear envelope to integrate within chromatin. Given the intimate association between chromatin and the nuclear envelope, we examined whether HIV-1 appropriates nuclear envelope components during infection. Here we show that emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection. Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the nucleus but integration into chromatin was inefficient, and conversion of viral cDNA to non-functional episomal cDNA increased. HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with chromatin was dependent on emerin. Barrier-to-autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA with emerin and for the ability of emerin to support virus infection. Therefore emerin, which bridges the interface between the inner nuclear envelope and chromatin, may be necessary for chromatin engagement by viral cDNA before integration.

Cells, Cultured↗
PubMed1988

Functional dissection of nuclear envelope mRNA translocation system: effects of phorbol ester and a monoclonal antibody recognizing cytoskeletal structures.

Unidirectional transport of poly(A)-containing mRNA [poly(A)+ mRNA] through the nuclear envelope pore complex is thought to be an energy (ATP or GTP)-dependent process which involves a nuclear envelope nucleoside triphosphatase (NTPase). In the intact envelope, this enzyme is regulatable by poly(A) binding and by poly(A)-dependent phosphorylation/dephosphorylation of other components of the mRNA translocation system, which are as yet unidentified. Monoclonal antibodies (mAbs) were elicited against the poly(A) binding nuclear envelope fraction isolated from rat liver. The mAbs were screened for their modulatory effects on mRNA transport in vitro. One stable clone decreased the efflux of rapidly labeled RNA and of one specific mRNA (ovalbumin) from isolated nuclei. It increased the binding of poly(A) to the envelope and increased the maximal catalytic rate of the NTPase, but it did not alter the apparent Km of the enzyme or the extent of its stimulation by poly(A). The nuclear envelope-associated protein kinase that down-regulates the NTPase was inhibited by the antibody, while other protein kinases were not affected. Because both the NTPase and mRNA efflux were inhibited by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, the sensitive kinase is probably protein kinase C. Protein kinase C was found to be associated with the isolated nuclear envelope. The antibody reacted with both a Mr 83,000 and a Mr 65,000 nuclear envelope polypeptide from rat liver and other tissues. By immunofluorescence microscopy in CV-1 cells, the antibody localized to the nuclear envelope and, in addition, to cytoplasmic filaments which show some superposition with the microfilament network.

Adenosine Triphosphate↗
PubMed2004

The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber.

Mechanical properties of the nuclear envelope have implications for cell and nuclear architecture as well as gene regulation. Using isolated Xenopus oocyte nuclei, we have established swelling conditions that separate the intact nuclear envelope (membranes, pore complexes and underlying lamin filament network) from nucleoplasm and the majority of chromatin. Swelling proves reversible with addition of high molecular mass dextrans. Micropipette aspiration of swollen and unswollen nuclear envelopes is also reversible and yields a network elastic modulus, unaffected by nucleoplasm, that averages 25 mN/m. Compared to plasma membranes of cells, the nuclear envelope is much stiffer and more resilient. Our results suggest that the nuclear lamina forms a compressed network shell of interconnected rods that is extensible but limited in compressibility from the native state, thus acting as a 'molecular shock absorber'. In light of the conservation of B-type lamins in metazoan evolution, the mechanical properties determined in this investigation suggest physical mechanisms by which mutated lamins can either destabilize nuclear architecture or influence nuclear responses to mechanical signals in Emery-Dreifuss muscular dystrophy, cardiomyopathy, progeria syndromes (premature 'aging') and other laminopathies.

Animals↗
PubMed1986

Diet fat alters the structure and function of the nuclear envelope: modulation of membrane fatty acid composition, NTPase activity and binding of triiodothyronine.

Mice were fed a diet either high or low in P/S ratio to determine the effect of altering dietary lipid on the fatty acid composition of liver nuclear envelopes and thereby on functions of the nuclear envelope. Mice fed the high P/S diet exhibited higher levels of C18:2 omega 6 and unsaturates in liver nuclear envelopes, higher specific activity of NTPase and specific binding for L-triiodothyronine at 15 degrees C and 22 degrees C compared with the low P/S diet fed group. These observations indicate that diet-induced differences in the fatty acid composition of nuclear envelope lipid affects functions of the nuclear envelope.

Animals↗
PubMed1987

Preparation and characterization of nuclear-envelope vesicles from rat liver nuclei.

We describe a procedure for the preparation of sealed nuclear-envelope vesicles from rat liver nuclei. These vesicles are strikingly similar in their polypeptide composition when compared with those of nuclear envelopes prepared conventionally using deoxyribonuclease I. Subfractionation analysis by means of extraction with high salt and urea show that the components of the nuclear envelope, e.g. the pore-complex/lamina fraction, are present. The residual DNA content is only 1.5%, and typical preparations consist of about 80% vesicles, with the vesicular character of these envelopes shown by microscopic and biochemical studies. The vesicles can be obtained in high yield, are tight and stable for at least two days and are enriched in a nucleoside triphosphatase thought to be involved in nucleocytoplasmic transport processes. Because the vesicles are largely free of components of the nuclear interior, but retain properties of intact nuclei, we believe that they are a valuable model system to study nucleocytoplasmic transport. Although in transport studies with isolated nuclei interference from intranuclear events has to be considered, the nuclear-envelope vesicles provide the possibility of studying translocation alone. Furthermore, the less complex nature of these vesicles compared with whole nuclei should facilitate investigation of the components involved in the regulation of nuclear transport processes.

Animals↗
PubMed1990

Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis.

We have identified autoantibodies from two patients with primary biliary cirrhosis (PBC) that recognize the nuclear envelope of mammalian cells on indirect immunofluorescence microscopy. These antibodies bind to a 58-kD integral membrane protein (p58) of the turkey erythrocyte nuclear envelope, which has been previously identified as a membrane receptor for lamin B (Worman, H. J., J. Yuan, G. Blobel, and S. D. Georgatos. 1988. Proc. Natl. Acad. Sci. USA. 85:8531). The antibodies also bind to a 61-kD integral membrane protein (p61) of the rat liver nuclear envelope. Affinity-purified antibodies eluted from turkey p58 bind to rat p61, showing that the two proteins share an epitope(s) and that p61 is likely the rat liver lamin B receptor. In human nuclear envelopes, the antigen recognized has an apparent molecular mass close to that of avian protein. These findings, along with the previous discovery of autoantibodies against an integral membrane glycoprotein (gp210) of the nuclear pore membrane in patients with PBC, suggest that antibodies against integral membrane proteins of the nuclear envelope are characteristic of a subset of patients with PBC.

Animals↗
PubMed1998

The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain.

LAP2 is an integral protein of the inner nuclear membrane which binds lamins and chromosomes and is suggested to have an important role in nuclear envelope organization. In a previous study we identified an internal 76-amino acid region of LAP2 which is required for stable targeting of the protein to the nuclear envelope. Here, we have mapped the lamin binding region of LAP2 and demonstrate that it coincides with this nuclear envelope targeting domain. In contrast, we found that the portion of LAP2 involved in binding to chromosomes resides in a separate region of the protein near its NH2 terminus. The minimal lamin binding region of LAP2 is capable of conferring stable nuclear envelope localization when attached to the transmembrane and partial lumenal domains of a protein that shows no nuclear envelope targeting activity. This directly supports the notion that a major mechanism for localization of integral membrane proteins at the inner nuclear membrane involves binding to lamins, which would constrain diffusion through the continuous nuclear envelope/endoplasmic reticulum membrane system.

Binding Sites↗
PubMed1999

Matrix attachment region binding protein MFP1 is localized in discrete domains at the nuclear envelope.

Recently, it has been suggested that nuclear processes, such as replication, transcription, and splicing, are spatially organized and associated with a nuclear framework called the nuclear matrix, a structure of unknown molecular composition. It has been shown that chromatin is attached to the nuclear matrix via specific DNA fragments called matrix attachment regions (MARs). We have begun to dissect the plant nuclear matrix by isolating a DNA binding protein with specific affinity for MARs. Here, it is shown that MAR binding filament-like protein 1 (MFP1) is associated with specklelike structures at the nuclear periphery that are part of isolated nuclei and the nuclear matrix. A predicted N-terminal transmembrane domain is necessary for the specific targeting of MFP1 to the speckles, indicating an association with the nuclear envelope-endoplasmic reticulum continuum. In addition, it is shown that a marker protein for plant microtubule organizing centers, which has been shown to be localized on the outside of the plant nuclear envelope, is also part of the nuclear matrix. These findings indicate a close and previously undescribed connection in plants between the nuclear envelope and the internal nuclear matrix, and they suggest a function for MFP1 in attaching chromatin to specific sites at the nuclear periphery.

Arabidopsis Proteins↗
PubMed2001

Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane.

The nuclear envelope (NE) is one of the least characterized structures of eukaryotic cells. The study of its functional roles is hampered by the small number of proteins known to be specifically located to it. Here, we present a comprehensive characterization of the NE proteome. We applied different fractionation procedures and isolated protein subsets derived from distinct NE compartments. We identified 148 different proteins by 16-benzyl dimethyl hexadecyl ammonium chloride (16-BAC) gel electrophoresis and matrix-assisted laser desorption ionization (MALDI) mass spectrometry; among them were 19 previously unknown or noncharacterized. The identification of known proteins in particular NE fractions enabled us to assign novel proteins to NE substructures. Thus, our subcellular proteomics approach retains the screening character of classical proteomic studies, but also allows a number of predictions about subcellular localization and interactions of previously noncharacterized proteins. We demonstrate this result by showing that two novel transmembrane proteins, a 100-kDa protein with similarity to Caenorhabditis elegans Unc-84A and an unrelated 45-kDa protein we named LUMA, reside in the inner nuclear membrane and likely interact with the nuclear lamina. The utility of our approach is not restricted to the investigation of the NE. Our approach should be applicable to the analysis of other complex membrane structures of the cell as well.

Animals↗
PubMed2004

Sorting out the nuclear envelope from the endoplasmic reticulum.

Although the interphase nuclear envelope is continuous with the endoplasmic reticulum, it is distinct from the endoplasmic reticulum in both form and composition. In metazoans, the nuclear envelope breaks down during mitosis and is thought to be completely reabsorbed by the endoplasmic reticulum. How these near neighbours are sorted out at the end of mitosis is an interesting mystery.

Animals↗
PubMed2000

Nuclear envelope fission is linked to cytokinesis in budding yeast.

We have investigated the relationship between nuclear envelope fission and cytokinesis during mitotic cell division in budding yeast. By carrying out time-lapse and optical sectioning video microscopy analysis of cells that express green fluorescent protein (GFP)-tagged nuclear envelope and actomyosin ring components, we found that nuclear division is temporally coupled to cytokinesis. Light and electron microscopy analysis also showed that nuclear envelope fission and the division of the nucleoplasm are severely delayed in cytokinesis mutants, resulting in discoupling between the nuclear division cycle and the budding cycle. These results suggest that homotypic membrane fusion may be activated by components or the mechanical action of cytokinetic structures and presents a mechanism for the equal partitioning of the nucleus and the temporal coordination of this event with chromosome segregation during mitosis.

Cell Division↗
PubMed1993

Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation.

Lamina-associated polypeptides (LAPs) 1A, 1B, 1C, and 2 are integral membrane proteins of the nuclear envelope associated with the nuclear lamina. Using in vitro assays, we show that LAPs 1A and 1B specifically bind to both lamins A and C and lamin B1, while LAP 2 associates only with lamin B1. LAP 2 also binds to mitotic chromosomes. The LAPs are phosphorylated during mitosis, and phosphorylation of LAP 2 by mitotic cytosol inhibits its binding to both lamin B1 and chromosomes. During late anaphase, LAP 2 associates with chromosomes prior to assembly of most lamins. Together, these data suggest that LAP 2 may have a key role in initial events of nuclear envelope reassembly, and that both LAP 2 and LAP 1 may be involved in attaching lamins to the nuclear envelope.

Animals↗
PubMed2004

Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope disease?

Facioscapulohumeral muscular dystrophy (FSHD) may be a new member of the class of neuromuscular diseases (NMD) due to defects in the nuclear envelope. Unlike other NMDs with primary defects in nuclear envelope proteins, however, FSHD may result from inappropriate chromatin interactions at the envelope. 3D Immuno-FISH and a novel method of 3D by 2D analysis using NucProfile were developed to examine nuclear organization of the FSHD genomic region. In contrast to most other telomeres, the FSHD region at 4q35.2 localizes to the nuclear periphery. This localization is consistent in normal myoblasts, myotubes, fibroblasts and lymphoblasts, does not vary significantly throughout the cell cycle, and is independent of chromosome territory effects. The nuclear lamina protein lamin A/C is required for FSHD region chromatin localization to the nuclear envelope, as the association is lost in lamin A/C null fibroblasts. As both normal and affected alleles (deleted for the subtelomeric repeat D4Z4) localize to the nuclear periphery, FSHD likely arises instead from improper interactions with transcription factors or chromatin modifiers at the nuclear envelope. Interestingly, it is not D4Z4 itself that mediates interaction with the envelope, as sequences proximal to D4Z4 (i.e. D4S139) localize closer to the nuclear periphery, perhaps accounting for the chromosome 4 specificity of the disease.

Chromatin↗
PubMedDate not supplied

Nuclear envelope proteins and chromatin arrangement: a pathogenic mechanism for laminopathies.

The involvement of the nuclear envelope in the modulation of chromatin organization is strongly suggested by the increasing number of human diseases due to mutations of nuclear envelope proteins. A common feature of these diseases, named laminopathies, is the occurrence of major chromatin defects. We previously reported that cells from laminopathic patients show an altered nuclear profile, and loss or detachment of heterochromatin from the nuclear envelope. Recent evidence indicates that processing of the lamin A precursor is altered in laminopathies featuring pre-mature aging and/or lipodystrophy phenotype. In these cases, pre-lamin A is accumulated in the nucleus and heterochromatin is severely disorganized. Here we report evidence indicating that pre-lamin A is mis-localized in the nuclei of Emery-Dreifuss muscular dystrophy fibroblasts, either bearing lamin A/C or emerin mutations. Abnormal pre-lamin A-containing structures are formed following treatment with a farnesyl-transferase inhibitor, a drug that causes accumulation of pre-lamin A. Pre-lamin A-labeled structures co-localize with heterochromatin clumps. These data indicate that in almost all laminopathies the expression of the mutant lamin A precursor disrupts the organization of heterochromatin domains. Our results further show that the absence of emerin expression alters the distribution of pre-lamin A and of heterochromatin areas, suggesting a major involvement of emerin in pre-lamin A-mediated mechanisms of chromatin remodeling.

Aging, Premature↗