Review: Nuclear Lamins—Structural Proteins with Fundamental Functions

Gruenbaum, Yosef; Wilson, Katherine L.; Harel, Amnon; Goldberg, Michal; Cohen, Merav

doi:10.1006/jsbi.2000.4216

Cited by 182 publications

(131 citation statements)

References 127 publications

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“…The nuclear lamina provides structural support for the nuclear membrane and attachment sites for chromatin. It is also required for a variety of essential cellular functions, including nuclear assembly following mitosis, DNA replication, and transcription (11,29).The nuclear lamina is composed primarily of type V intermediate filament proteins known as lamins. Lamin structure is conserved in multicellular eukaryotes, and individual lamin filaments consist of multiple coiled-coil dimers linked in a head-to-tail fashion.…”

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confidence: 99%

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Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Reynolds

Liang

Baines

2004

J Virol

157

209

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The herpes simplex virus type 1 (HSV-1) U L 31 and U L 34 proteins are dependent on each other for proper targeting to the nuclear membrane and are required for efficient envelopment of nucleocapsids at the inner nuclear membrane. In this work, we show that whereas the solubility of lamins A and C (lamin A/C) was not markedly increased, HSV induced conformational changes in the nuclear lamina of infected cells, as viewed after staining with three different lamin A/C-specific antibodies. In one case, reactivity with a monoclonal antibody that recognizes an epitope in the lamin tail domain was greatly reduced in HSV-infected cells. This apparent HSV-induced epitope masking required both U L 31 and U L 34, but these proteins were not sufficient to mask the epitope in uninfected cells, indicating that other HSV proteins are also required. In the second case, staining with a rabbit polyclonal antibody that primarily recognizes epitopes in the lamin A/C rod domain revealed that U L 34 is required for HSV-induced decreased availability of epitopes for reaction with the antibody, whereas U L 31 protein was dispensable for this effect. Still another polyclonal antibody indicated virtually no difference in lamin A/C staining in infected versus uninfected cells, indicating that the HSVinduced changes are more conformational than the result of lamin depletion at the nuclear rim. Further evidence supporting an interaction between the nuclear lamina and the U L 31/U L 34 protein complex includes the observations that (i) overexpression of the U L 31 protein in uninfected cells was sufficient to relocalize lamin A/C from the nuclear rim into nucleoplasmic aggregates, (ii) overexpression of U L 34 was sufficient to relocalize some lamin A/C into the cytoplasm, and (iii) both U L 31 and U L 34 could directly bind lamin A/C in vitro. These studies suggest that the U L 31 and U L 34 proteins modify the conformation of the nuclear lamina in infected cells, possibly by direct interaction with lamin A/C, and that other proteins are also likely involved. Given that the nuclear lamina potentially excludes nucleocapsids from envelopment sites at the inner nuclear membrane, the lamina alteration may reflect a role of the U L 31/U L 34 protein complex in perturbing the lamina to promote nucleocapsid egress from the nucleus. Alternatively, the data are compatible with a role of the lamina in targeting the U L 31/U L 34 protein complex to the nuclear membrane.The nuclear envelope consists of two leaflets, defined as the inner nuclear membrane and outer nuclear membrane. The perinuclear space, defined as the space between the two leaflets, is continuous with the lumen of the endoplasmic reticulum. A network of predominantly insoluble cellular proteins, the nuclear lamina, lines the nucleoplasmic face of the inner nuclear membrane. The nuclear lamina provides structural support for the nuclear membrane and attachment sites for chromatin. It is also required for a variety of essential cellular functions, including nuclear assembly following mi...

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confidence: 99%

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Reynolds

Liang

Baines

2004

J Virol

157

209

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“…The range of regulatory functions performed by INM proteins is widened further by the recent discovery that Lap2␤ and emerin interact directly with a transcription repressor, Germ Cell-less (18,19), and that emerin binds in vitro to a splicing-associated factor, YT521-B (20). The discovery that mutations in lamin A/C and emerin are implicated in EmeryDreyfuss muscular dystrophy (21)(22)(23), and a growing spectrum of human diseases has sparked a resurgence of interest in the lamina/nuclear envelope interface. Collectively, these diseases are now termed "laminopathies" (24 -26).…”

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confidence: 99%

Sun2 Is a Novel Mammalian Inner Nuclear Membrane Protein

Hodzic

Yeater

Bengtsson

et al. 2004

Journal of Biological Chemistry

189

202

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Sun protein (Sun1 and Sun2) cDNAs were previously cloned based on the homology of their C-terminal regions (SUN (Sad1 and UNC) domain) with the Caenorhabditis elegans protein UNC-84 whose mutation disrupts nuclear migration/positioning. In this study, we raised an anti-Sun2 serum and identified Sun2 in mammalian cells. In HeLa cells, Sun2 displays a nuclear rim-like pattern typical for a nuclear envelope protein. The Sun2 antibody signal co-localizes with nuclear pore and INM markers signals. The rim-like pattern was also observed with the recombinant full-length Sun2 protein fused to either EGFP or V5 epitopes. In addition, we found that a recombinant truncated form of Sun2, extending from amino acids 26 to 339, is sufficient to specify the nuclear envelope localization. Biochemical analyses show that Sun2 is an 85-kDa protein that is partially insoluble in detergent with high salt concentration and in chaotropic agents. Furthermore, Sun2 is enriched in purified HeLa cell nuclei. Electron microscopy analysis shows that Sun2 localizes in the nuclear envelope with a subpopulation present in small clusters. Additionally, we show that the SUN domain of Sun2 is localized to the periplasmic space between the inner and the outer nuclear membranes. From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein.Because the SUN domain is conserved from fission yeast to mammals, we suggest that Sun2 belongs to a new class of nuclear envelope proteins with potential relevance to nuclear membrane function in the context of the involvement of its components in an increasing spectrum of human diseases.In eukaryotic cells, the nuclear envelope, which separates the nucleoplasm from the cytoplasm, is composed of the inner and outer nuclear membranes (INM 1 and ONM, respectively), the latter membrane being continuous with the endoplasmic reticulum. The two membranes are separated by a thin lumen and are joined at nuclear pores (1-3). Underlying the INM is a meshwork of various lamin isoforms (4) that are in close contact with the INM and its resident proteins (5). Characterized INM proteins in mammalian cells include the lamin B receptor (6), lamin-associated polypeptides 1 and 2 (Lap1 and Lap2) (7), emerin (8), and Man1 (9). These proteins possess a hydrophilic N-terminal region that protrudes into the nucleoplasm as well as one or more hydrophobic regions leading to predicted single or multispanning transmembrane domains. INM proteins are immobilized in the nuclear envelope through their interaction with lamins and/or heterochromatin (10, 11).Beside their structural role, lamina components also exert additional functions through their ability to interact with effector proteins involved in various regulatory processes. For example, the lamin B receptor directly binds to HP1 (12), a heterochromatin protein involved in transcription repression. Lap2 (13,14), emerin (15), and Man1 (16) interact with the barrier-to-autointegration factor, a 10-kDa DNA-binding protein (17). The range of regulatory functions pe...

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“…The primary components of the nuclear lamina are intermediate filament (IF) lamins and in particular lamin B1, which is constitutively expressed (2,3). Human lamin B1 mutated by deletion of the rod domain (B1⌬rod) causes severe alteration of the nuclear lamina organization (4 -6), which suggests that lamin B1 plays a key role in the structural integrity of the NE (7). Lamins and many other NE proteins are subject to mitotic phosphorylation by the Cdc2 kinase, which diminishes proteinprotein interactions required for NE integrity, dispersing structural proteins into the cytoplasm at mitosis (8).…”

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Nuclear Envelope Breakdown Requires Overcoming the Mechanical Integrity of the Nuclear Lamina

Panorchan¹,

Schafer²,

Wirtz

et al. 2004

Journal of Biological Chemistry

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In prophase cells, lamin B1 is the major component of the nuclear lamina, a filamentous network underlying the nucleoplasmic side of the nuclear membrane, whereas lamin A/C is dissociated from the scaffold. In vivo fluorescence microscopy studies have shown that, during the G 2 /M transition, the first gap in the nuclear envelope (NE) appears before lamin B1 disassembly and is caused by early spindle microtubules impinging on the NE. This result suggests that the mechanical tearing of the NE by microtubules plays a central role to the progression of mitosis. To investigate whether this microtubule-induced NE deformation is sufficient for NE breakdown, we assess the mechanical resilience of a reconstituted lamin B1 network. Quantitative rheological methods demonstrate that human lamin B1 filaments form stiff networks that can resist much greater deformations than those caused by microtubules impinging on the NE. Moreover, lamin B1 networks possess an elastic stiffness, which increases under tension, and an exceptional resilience against shear deformations. These results demonstrate that both mechanical tearing of the lamina and biochemical modification of lamin B1 filaments are required for NE breakdown.The nuclear lamina is a filamentous meshwork underlying the nucleoplasmic side of the nuclear envelope (NE) 1 (1). The primary components of the nuclear lamina are intermediate filament (IF) lamins and in particular lamin B1, which is constitutively expressed (2, 3). Human lamin B1 mutated by deletion of the rod domain (B1⌬rod) causes severe alteration of the nuclear lamina organization (4 -6), which suggests that lamin B1 plays a key role in the structural integrity of the NE (7). Lamins and many other NE proteins are subject to mitotic phosphorylation by the Cdc2 kinase, which diminishes proteinprotein interactions required for NE integrity, dispersing structural proteins into the cytoplasm at mitosis (8). In particular, a lamin B1 mutant lacking the Cdc2 kinase phosphorylation site prevents NE breakdown (9 -11), which suggests that lamin phosphorylation is a prerequisite for NE destabilization before mitosis (12).Nevertheless, there is growing evidence in vitro and in vivo that lamin B1 disassembly is independent of NE breakdown. Lamin B1 solubilization in vitro has been shown to occur without NE breakdown (13). Time-resolved fluorescence microscopy reveals that the organization of green fluorescent proteinlamins in the NE of live cells remains intact until NE breakdown and little soluble lamin (Ͻ5%) can be detected through fluorescence after recovery before NE breakdown (14). Instead, early spindle microtubules cause folds in the NE, which develop into deep invaginations that create an initial hole in the NE (15). This hole forms at a specific NE position, which is distal from the centrosomes (14). The non-random position of the hole on the NE surface argues against weakening of the lamina by lamin disassembly prior to NE breakdown, which would create randomly located holes wherever lamin is completely disass...

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Review: Nuclear Lamins—Structural Proteins with Fundamental Functions

Cited by 182 publications

References 127 publications

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Sun2 Is a Novel Mammalian Inner Nuclear Membrane Protein

Nuclear Envelope Breakdown Requires Overcoming the Mechanical Integrity of the Nuclear Lamina

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Review: Nuclear Lamins—Structural Proteins with Fundamental Functions

Cited by 182 publications

References 127 publications

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U L 31 and U L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U L 31 and U L 34

Sun2 Is a Novel Mammalian Inner Nuclear Membrane Protein

Nuclear Envelope Breakdown Requires Overcoming the Mechanical Integrity of the Nuclear Lamina

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Product

Resources

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Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes U _L 31 and U _L 34