Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.

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The Torsin/ NEP1R1-CTDNEP1/ Lipin axis regulates nuclear envelope lipid metabolism for nuclear pore complex insertion

10.1101/2020.07.05.188599 ◽

2020 ◽

Author(s):

Julie Jacquemyn ◽

Joyce Foroozandeh ◽

Katlijn Vints ◽

Jef Swerts ◽

Patrik Verstreken ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Nuclear Envelope ◽

Nuclear Pore Complex ◽

Lipid Droplets ◽

Nuclear Pore ◽

List Type ◽

Unknown Mechanism ◽

Structure Lipid ◽

Cellular Events ◽

Upstream Regulator

AbstractTorsin ATPases of the endoplasmic reticulum (ER) and nuclear envelope (NE) lumen inhibit Lipin-mediated phosphatidate (PA) to diacylglycerol (DAG) conversion by an unknown mechanism. This excess PA metabolism is implicated in TOR1A/TorsinA diseases, but it is unclear whether it explains why Torsin concomitantly affects nuclear structure, lipid droplets (LD), organelle and cell growth. Here a fly miniscreen identified that Torsins affect these events via the NEP1R1-CTDNEP1 phosphatase complex. Further, Torsin homo-oligomerization rather than ATPase activity was key to function. NEP1R1-CTDNEP1 activates Lipin by dephosphorylation. We show that Torsin prevents CTDNEP1 from accumulating in the NE and excludes Lipin from the nucleus. Moreover, this repression of nuclear PA metabolism is required for interphase nuclear pore biogenesis. We conclude that Torsin is an upstream regulator of the NEP1R1-CTDNEP1/ Lipin pathway. This connects the ER/NE lumen with PA metabolism, and affects numerous cellular events including it has a previously unrecognized role in nuclear pore biogenesis.HighlightsNuclear envelope PA-DAG-TAG synthesis is independently regulated by Torsin and Torip/LAP1Torsin removes CTDNEP1 from the nuclear envelope and excludes Lipin from the nucleusExcess nuclear envelope NEP1R1-CTDNEP1/ Lipin activity impairs multiple aspects of NPC biogenesisNEP1R1-CTDNEP1/ Lipin inhibition prevents cellular defects associated with TOR1A and TOR1AIP1 / LAP1 disease

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Selective Nuclear Pore Complex Removal Drives Nuclear Envelope Division in Fission Yeast

Current Biology ◽

10.1016/j.cub.2020.05.066 ◽

2020 ◽

Vol 30 (16) ◽

pp. 3212-3222.e2 ◽

Cited By ~ 2

Author(s):

María Expósito-Serrano ◽

Ana Sánchez-Molina ◽

Paola Gallardo ◽

Silvia Salas-Pino ◽

Rafael R. Daga

Keyword(s):

Nuclear Envelope ◽

Fission Yeast ◽

Nuclear Pore Complex ◽

Nuclear Pore

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NUCLEAR MEMBRANES FROM MAMMALIAN LIVER

The Journal of Cell Biology ◽

10.1083/jcb.46.2.379 ◽

1970 ◽

Vol 46 (2) ◽

pp. 379-395 ◽

Cited By ~ 142

Author(s):

Werner W. Franke ◽

Barbara Deumling ◽

Baerbel Ermen ◽

Ernst-Dieter Jarasch ◽

Hans Kleinig

Keyword(s):

Endoplasmic Reticulum ◽

Nuclear Envelope ◽

Nuclear Membrane ◽

Cytochrome B5 ◽

Buoyant Density ◽

Nuclear Pore ◽

Nuclear Membranes ◽

Dna And Rna ◽

Mammalian Liver ◽

Order Of Magnitude

Nuclear membranes were isolated from rat and pig liver by sonication of highly purified nuclear fractions and subsequent removal of adhering nucleoproteins in a high salt medium. The fractions were examined in the electron microscope by both negative staining and thin sectioning techniques and were found to consist of nuclear envelope fragments of widely varying sizes. Nuclear pore complex constituents still could frequently be recognized. The chemical composition of the nuclear membrane fractions was determined and compared with those of microsomal fractions prepared in parallel. For total nuclei as well as for nuclear membranes and microsomes, various enzyme activities were studied. The results indicate that a similarity exists between both fractions of cytomembranes, nuclear envelope, and endoplasmic reticulum, with respect to their RNA:protein ratio and their content of polar and nonpolar lipids. Both membranous fractions had many proteins in common including some membrane-bound enzymes. Activities in Mg-ATPase and the two examined cytochrome reductases were of the same order of magnitude. The content of cytochrome b5 as well as of P-450 was markedly lower in the nuclear membranes. The nuclear membranes were found to have a higher buoyant density and to be richer in protein. The glucose-6-phosphatase and Na-K-ATPase activities in the nuclear membrane fraction were very low. In the gel electrophoresis, in addition to many common protein bands, some characteristic ones for either microsomal or nuclear membranous material were detected. Significant small amounts of DNA and RNA were found to remain closely associated with the nuclear envelope fragments. Our findings indicate that nuclear and endoplasmic reticulum membranes which are known to be in morphological continuity have, besides a far-reaching similarity, some characteristic differences.

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Nuclear envelope starts with a clean sheet

The Journal of Cell Biology ◽

10.1083/jcb.1943if ◽

2011 ◽

Vol 194 (3) ◽

pp. 351-351

Author(s):

Ben Short

Keyword(s):

Nuclear Envelope ◽

Nuclear Pore Complex ◽

Nuclear Pore ◽

Nuclear Membranes

After mitosis, nuclear membranes form directly from ER cisternae before nuclear pore complex reassembly.

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Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22084165 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4165

Author(s):

Baojin Ding ◽

Masood Sepehrimanesh

Keyword(s):

Neurodegenerative Diseases ◽

Nuclear Envelope ◽

Nuclear Pore Complex ◽

Molecular Mechanisms ◽

Nucleocytoplasmic Transport ◽

Research Field ◽

Regulatory Mechanisms ◽

Nuclear Pore ◽

Age Related ◽

Lateral Sclerosis

Nucleocytoplasmic transport (NCT) across the nuclear envelope is precisely regulated in eukaryotic cells, and it plays critical roles in maintenance of cellular homeostasis. Accumulating evidence has demonstrated that dysregulations of NCT are implicated in aging and age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and Huntington disease (HD). This is an emerging research field. The molecular mechanisms underlying impaired NCT and the pathogenesis leading to neurodegeneration are not clear. In this review, we comprehensively described the components of NCT machinery, including nuclear envelope (NE), nuclear pore complex (NPC), importins and exportins, RanGTPase and its regulators, and the regulatory mechanisms of nuclear transport of both protein and transcript cargos. Additionally, we discussed the possible molecular mechanisms of impaired NCT underlying aging and neurodegenerative diseases, such as ALS/FTD, HD, and AD.

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ON THE ATTACHMENT OF THE NUCLEAR PORE COMPLEX

The Journal of Cell Biology ◽

10.1083/jcb.62.3.746 ◽

1974 ◽

Vol 62 (3) ◽

pp. 746-754 ◽

Cited By ~ 102

Author(s):

Robert Peter Aaronson ◽

Günter Blobel

Keyword(s):

Nuclear Envelope ◽

Nuclear Pore Complex ◽

Structural Integrity ◽

Polyacrylamide Gel Electrophoresis ◽

Complete Removal ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Nuclear Membranes ◽

Peripheral Heterochromatin ◽

Pore Complexes

Electron microscope examination of isolated rat liver nuclei after treatment with the detergent Triton X-100 revealed the complete removal of both the inner and outer membranes of the nuclear envelope. The envelope-denuded nuclei did not show any change in either shape or internal ultrastructure. Most strikingly, the nuclear pore complexes, which in untreated nuclei appear to be integral components of the nuclear envelope, were retained in their characteristic location at the distal ends of the channels leading through the peripheral heterochromatin. Determination of the chemical composition of detergent-treated nuclei showed that over 95% of the nuclear phospholipid was solubilized, thus corroborating the morphological absence of nuclear membranes. Furthermore, detergent treatment also solubilized approximately 10% of the nuclear protein. Analysis of the solubilized protein by polyacrylamide gel electrophoresis in the presence of SDS indicated that these proteins belong to a few specific classes which presumably represent the major polypeptides of the nuclear membranes. The total absence of the nuclear envelope on both morphological and biochemical grounds supports the idea that the nuclear pore complex does not require the membranes either for attachment to the nucleus or for maintenance of its own structural integrity.

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Nuclear pore complex glycoproteins contain cytoplasmically disposed O-linked N-acetylglucosamine.

The Journal of Cell Biology ◽

10.1083/jcb.104.5.1157 ◽

1987 ◽

Vol 104 (5) ◽

pp. 1157-1164 ◽

Cited By ~ 254

Author(s):

G D Holt ◽

C M Snow ◽

A Senior ◽

R S Haltiwanger ◽

L Gerace ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Nuclear Envelope ◽

Rat Liver ◽

Nuclear Pore Complex ◽

Nuclear Pore ◽

Side Chains ◽

Nuclear Membranes ◽

Cell Biol ◽

Direct Demonstration ◽

Polypeptide Backbone

A novel form of protein-saccharide linkage consisting of single N-acetylglucosamine (GlcNAc) residues attached in O-linkages directly to the polypeptide backbone has been described (Holt, G. D., and G. W. Hart, 1986, J. Biol. Chem., 261:8049-8057). This modification was found on proteins distributed throughout the cell, although proteins bearing O-linked GlcNAc moieties were particularly abundant in the cytosolic and nuclear envelope fractions of rat liver. In the accompanying article (Snow, C. M., A. Senior, and L. Gerace, 1987, J. Cell. Biol., 104: 1143-1156), the authors describe monoclonal antibodies directed against eight proteins localized to the nuclear pore complex. These proteins occur on the cytoplasmic and nucleoplasmic (but not lumenal) sides of nuclear membranes. In this report, we demonstrate that all members of this group of pore complex proteins bear multiple O-linked GlcNAc residues. Further, we show that the O-linked GlcNAc moieties are linked via serine (and possibly threonine) side chains to these proteins. Perturbing the O-linked GlcNAc residues either by covalently attaching galactose to them or by releasing them with beta-N-acetylglucosaminidase strongly diminishes the immunoreactivity of the proteins with all of the monoclonal antibodies. However, the O-linked GlcNAc moieties are only part of the epitopes recognized, since O-GlcNAc-containing limit pronase fragments of nuclear pore complex proteins cannot be immunoprecipitated by these antibodies. These findings, taken together with those in the accompanying article, are a direct demonstration that proteins of the cytoplasm and nucleoplasm bear O-linked GlcNAc residues.

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POM121 and Sun1 play a role in early steps of interphase NPC assembly

The Journal of Cell Biology ◽

10.1083/jcb.201012154 ◽

2011 ◽

Vol 194 (1) ◽

pp. 27-37 ◽

Cited By ~ 90

Author(s):

Jessica A. Talamas ◽

Martin W. Hetzer

Keyword(s):

Cell Cycle ◽

Nuclear Envelope ◽

Nuclear Membrane ◽

Molecular Mechanisms ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Outer Nuclear Membrane ◽

Nuclear Membranes ◽

Distinct Cell ◽

Pore Complexes

Nuclear pore complexes (NPCs) assemble at the end of mitosis during nuclear envelope (NE) reformation and into an intact NE as cells progress through interphase. Although recent studies have shown that NPC formation occurs by two different molecular mechanisms at two distinct cell cycle stages, little is known about the molecular players that mediate the fusion of the outer and inner nuclear membranes to form pores. In this paper, we provide evidence that the transmembrane nucleoporin (Nup), POM121, but not the Nup107–160 complex, is present at new pore assembly sites at a time that coincides with inner nuclear membrane (INM) and outer nuclear membrane (ONM) fusion. Overexpression of POM121 resulted in juxtaposition of the INM and ONM. Additionally, Sun1, an INM protein that is known to interact with the cytoskeleton, was specifically required for interphase assembly and localized with POM121 at forming pores. We propose a model in which POM121 and Sun1 interact transiently to promote early steps of interphase NPC assembly.

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