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https://www.readbyqxmd.com/read/29784648/mouse-models-of-nesprin-related-diseases
#1
REVIEW
Can Zhou, Li Rao, Derek T Warren, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29782140/fluorescent-labeling-of-the-nuclear-envelope-by-localizing-gfp-on-the-inner-nuclear-membrane
#2
Toshiyuki Taniyama, Natsumi Tsuda, Shinji Sueda
The nuclear envelope (NE) is a double membrane that segregates nuclear components from the cytoplasm in eukaryote cells. It is well-known that the NE undergoes a breakdown and reformation during mitosis in animal cells. However, the detailed mechanisms of the NE dynamics are not yet fully understood. Here, we propose a method for the fluorescent labeling of the NE in living cells, which enables the tracing of the NE dynamics during cell division under physiological conditions. In our method, labeling of the NE is accomplished by fixing green fluorescent protein carrying the nuclear localization signal on the inner nuclear membrane based on a unique biotinylation reaction from the archaeon Sulfolobus tokodaii...
May 21, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29777038/mechanical-stability-of-the-cell-nucleus-roles-played-by-the-cytoskeleton-in-nuclear-deformation-and-strain-recovery
#3
Xian Wang, Haijiao Liu, Min Zhu, Changhong Cao, Zhensong Xu, Yonit Tsatskis, Kimberly Lau, Chikin Kuok, Tobin Filleter, Helen McNeill, Craig A Simmons, Sevan Hopyan, Yu Sun
Extracellular forces transmitted through the cytoskeleton can deform the cell nucleus. Large nuclear deformation increases the risk of disrupting the nuclear envelope's integrity and causing DNA damage. Mechanical stability of the nucleus defines its capability of maintaining nuclear shape by minimizing nuclear deformation and recovering strain when deformed. Understanding the deformation and recovery behavior of the nucleus requires characterization of nuclear viscoelastic properties. Here, we quantified the decoupled viscoelastic parameters of the cell membrane, cytoskeleton, and the nucleus...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29776970/the-e3-ubiquitin-ligase-mib-1-is-necessary-to-form-the-nuclear-halo-in-caenorhabditis-elegans-sperm
#4
Leslie A Herrera, Daniel A Starr
Unlike the classical nuclear envelope with two membranes found in other eukaryotic cells, most nematode sperm nuclei are not encapsulated by membranes. Instead, they are surrounded by a nuclear halo of unknown composition. How the halo is formed and regulated is unknown. We used forward genetics to identify molecular lesions behind three classical fer (fertilization defective) mutations that disrupt the ultrastructure of the Caenorhabditis elegans sperm nuclear halo. We found fer-2 and fer-4 alleles to be nonsense mutations in mib-1...
May 18, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29767962/targeting-photo-induced-dna-destruction-by-ru-ii-tetraazaphenathrene-in-live-cells-by-signal-peptide
#5
Christopher S Burke, Aisling Byrne, Tia E Keyes
Exploiting NF-κB transcription factor peptide conjugation, a Ru(II)-bis-tap complex (tap = 1,4,5,8-tetraazaphenanthrene) was targeted specifically to the nuclei of live mammalian (HeLa and CHO) cells for the first time. DNA binding in the nucleus of live cells was evident from gradual extinction of the metal complex luminescence after it had crossed the nuclear envelope, attributed to guanine quenching of the ruthenium emission via photoinduced electron transfer. Resonance Raman imaging confirmed that the complex remained in the nucleus after emission is extinguished...
May 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29757287/combinational-treatment-of-trichostatin-a-and-vitamin-c-improves-the-efficiency-of-cloning-mice-by-somatic-cell-nuclear-transfer
#6
Rika Azuma, Kei Miyamoto, Mami Oikawa, Masayasu Yamada, Masayuki Anzai
Somatic cell nuclear transfer (SCNT) provides a unique opportunity to directly produce a cloned animal from a donor cell, and it requires the use of skillful techniques. Additionally, the efficiencies of cloning have remained low since the successful production of cloned animals, especially mice. There have been many attempts to improve the cloning efficiency, and trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to enhance the efficiency of cloning. Here, we report a dramatically improved cloning method in mice...
April 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29757215/the-rules-and-functions-of-nucleocytoplasmic-shuttling-proteins
#7
REVIEW
Xuekun Fu, Chao Liang, Fangfei Li, Luyao Wang, Xiaoqiu Wu, Aiping Lu, Guozhi Xiao, Ge Zhang
Biological macromolecules are the basis of life activities. There is a separation of spatial dimension between DNA replication and RNA biogenesis, and protein synthesis, which is an interesting phenomenon. The former occurs in the cell nucleus, while the latter in the cytoplasm. The separation requires protein to transport across the nuclear envelope to realize a variety of biological functions. Nucleocytoplasmic transport of protein including import to the nucleus and export to the cytoplasm is a complicated process that requires involvement and interaction of many proteins...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29754147/non-senescent-hydra-tolerates-severe-disturbances-in-the-nuclear-lamina
#8
Alexander Klimovich, Arvid Rehm, Jörg Wittlieb, Eva-Maria Herbst, Ricardo Benavente, Thomas C G Bosch
The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization...
May 10, 2018: Aging
https://www.readbyqxmd.com/read/29750601/allelic-heterogeneity-of-lamin-a-c-phenotypes-and-molecular-mechanism-behind-it
#9
Jelena Perovanovic, Eric P Hoffman
Mutations in the LMNA gene cause a broad range of clinical syndromes that show tissue-restricted abnormalities of post mitotic tissues, such as muscle, nerve, heart, and adipose tissue. Mutations in other nuclear envelope proteins cause clinically overlapping disorders. The majority of mutations are dominant single amino acid changes (toxic protein produced by the single mutant gene), and patients are heterozygous with both normal and abnormal proteins. Experimental support has been provided for different models of cellular pathogenesis in nuclear envelope diseases, including changes in heterochromatin formation at the nuclear membrane (epigenomics), changes in the timing of steps during terminal differentiation of cells, and structural abnormalities of the nuclear membrane...
May 11, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29748517/duplication-and-nuclear-envelope-insertion-of-the-yeast-microtubule-organizing-centre-the-spindle-pole-body
#10
REVIEW
Diana Rüthnick, Elmar Schiebel
The main microtubule organizing centre in the unicellular model organisms Saccharomyces cerevisiae and Schizosaccharomyces pompe is the spindle pole body (SPB). The SPB is a multilayer structure, which duplicates exactly once per cell cycle. Unlike higher eukaryotic cells, both yeast model organisms undergo mitosis without breakdown of the nuclear envelope (NE), a so-called closed mitosis. Therefore, in order to simultaneously nucleate nuclear and cytoplasmic MTs, it is vital to embed the SPB into the NE at least during mitosis, similarly to the nuclear pore complex (NPC)...
May 10, 2018: Cells
https://www.readbyqxmd.com/read/29743377/equine-myxovirus-resistance-protein-2-restricts-lentiviral-replication-by-blocking-nuclear-uptake-of-capsid-protein
#11
Shuang Ji, Lei Na, Huiling Ren, Yujie Wang, Xiaojun Wang
Human Myxovirus resistance 2 (huMxB) has been shown to be a determinant type I interferon-induced host factor involved in the inhibition of HIV-1 as well as many other primate lentiviruses. This blocking occurs after the reverse transcription of viral RNA and ahead of the integration into the host DNA, which is closely connected to the ability of the protein to bind the viral capsid. To date, Mx2s derived from non-primate animals have shown no capacity for HIV-1 suppression. In this study, we examined the restrictive effect of equine Mx2 (eqMx2) on both the equine infectious anemia virus (EIAV) and HIV-1 and investigated possible mechanisms for its specific function...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29739751/dynamic-nuclear-envelope-phenotype-in-rats-overexpressing-mutated-human-torsina-protein
#12
Libo Yu-Taeger, Viktoria Gaiser, Larissa Lotzer, Tina Roenisch, Benedikt Timo Fabry, Janice Stricker-Shaver, Nicolas Casadei, Michael Walter, Martin Schaller, Olaf Riess, Huu Phuc Nguyen, Thomas Ott, Kathrin Grundmann-Hauser
A three-base-pair deletion in the human TOR1A gene is causative for the most common form of primary dystonia, the early-onset dystonia type 1 (DYT1 dystonia). The pathophysiological consequences of this mutation are still unknown.To study the pathology of the mutant torsinA (TOR1A) protein, we have generated a transgenic rat line that overexpresses the human mutant protein under the control of the human TOR1A promoter. This new animal model was phenotyped with several approaches, including behavioral tests and neuropathological analyses...
May 8, 2018: Biology Open
https://www.readbyqxmd.com/read/29738835/immunolocalization-of-orexin-a-and-its-receptors-in-the-different-structures-of-the-porcine-ovary
#13
Luisa Ragionieri, Francesca Ravanetti, Rosanna Di Lecce, Maddalena Botti, Ciccimarra Roberta, Simona Bussolati, Giuseppina Basini, Ferdinando Gazza, Antonio Cacchioli
Orexins are neuropeptides with pleiotropic functions, involved in the coordination of multiple versatile physiological processes, in particular related to food intake and several aspects of the reproductive process. Their actions are carried out through the bond with the related Orexin 1 (OXR1) and Orexin 2 (OXR2) G-protein-coupled receptors. Studies on the expression of the orexinergic system in the female genital organs are scarce and limited to preovulatory gametogenic follicles and corpora lutea isolated from the rest of the ovary...
May 5, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/29733383/pde4-and-makap%C3%AE-are-nodal-organizers-of-%C3%AE-2-ars-nuclear-pka-signaling-in-cardiac-myocytes
#14
Ibrahim Bedioune, Florence Lefebvre, Patrick Lechêne, Audrey Varin, Valérie Domergue, Michael S Kapiloff, Rodolphe Fischmeister, Grégoire Vandecasteele
Aims: β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes. Methods and Results: We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation...
May 3, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29722648/distinct-safe-zones-at-the-nuclear-envelope-ensure-robust-replication-of-heterochromatic-chromosome-regions
#15
Hani Ebrahimi, Hirohisa Masuda, Devanshi Jain, Julia Promisel Cooper
Chromosome replication and transcription occur within a complex nuclear milieu whose functional subdomains are beginning to be mapped out. Here we delineate distinct domains of the fission yeast nuclear envelope (NE), focusing on regions enriched for the inner NE protein, Bqt4, or the lamin interacting domain protein, Lem2. Bqt4 is relatively mobile around the NE and acts in two capacities. First, Bqt4 tethers chromosome termini and the mat locus to the NE specifically while these regions are replicating. This positioning is required for accurate heterochromatin replication...
May 3, 2018: ELife
https://www.readbyqxmd.com/read/29706543/modulation-of-protein-interaction-states-through-the-cell-cycle
#16
Lingyun Dai, Tianyun Zhao, Xavier Bisteau, Wendi Sun, Nayana Prabhu, Yan Ting Lim, Radoslaw M Sobota, Philipp Kaldis, Pär Nordlund
Global profiling of protein expression through the cell cycle has revealed subsets of periodically expressed proteins. However, expression levels alone only give a partial view of the biochemical processes determining cellular events. Using a proteome-wide implementation of the cellular thermal shift assay (CETSA) to study specific cell-cycle phases, we uncover changes of interaction states for more than 750 proteins during the cell cycle. Notably, many protein complexes are modulated in specific cell-cycle phases, reflecting their roles in processes such as DNA replication, chromatin remodeling, transcription, translation, and disintegration of the nuclear envelope...
April 21, 2018: Cell
https://www.readbyqxmd.com/read/29694900/importin-%C3%AE-and-vnebd-control-meiotic-spindle-disassembly-in-fission-yeast
#17
Ignacio Flor-Parra, Ana Belén Iglesias-Romero, Silvia Salas-Pino, Rafael Lucena, Juan Jimenez, Rafael R Daga
In metazoans, the nuclear envelope (NE) breakdown (NEBD) occurs during "open" mitosis and meiosis. In the fission yeast Schizosaccharomyces pombe, the mitosis and the first meiotic division (MI) are "closed," during which the NE is maintained. Intriguingly, during the second meiotic division (MII), the NE is also maintained, but nuclear and cytoplasmic molecules are mixed similarly to open mitosis, a phenomenon of unknown biological significance called "virtual" NEBD (vNEBD). Here, we show that importin-α-dependent nucleocytoplasmic transport regulates spindle disassembly late in anaphase B at MI, as previously reported for mitosis...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29694899/to-make-a-long-spindle-short-nuclear-envelope-breakdown-during-meiosis
#18
Joseph M Varberg, Sue L Jaspersen
In fission yeast, the nuclear envelope (NE) remains intact during mitosis and meiosis I but is compromised during meiosis II. In this issue of Cell Reports, Flor-Parra et al. (2018) demonstrate that this NE alteration regulates meiosis II spindle disassembly and the ploidy of meiotic products.
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29691054/sun-mediated-mechanical-linc-between-nucleus-and-cytoskeleton-regulates-%C3%AE-catenin-nuclear-access
#19
Gunes Uzer, Guniz Bas, Buer Sen, Zhihui Xie, Scott Birks, Melis Olcum, Cody McGrath, Maya Styner, Janet Rubin
βcatenin acts as a primary intracellular signal transducer for mechanical and Wnt signaling pathways to control cell function and fate. Regulation of βcatenin in the cytoplasm has been well studied but βcatenin nuclear trafficking and function remains unclear. In a previous study we showed that, in mesenchymal stem cells (MSC), mechanical blockade of adipogenesis relied on inhibition of βcatenin destruction complex element GSK3β (glycogen synthase kinase 3β) to increase nuclear βcatenin as well as the function of Linker of Cytoskeleton and Nucleoskeleton (LINC) complexes, suggesting that these two mechanisms may be linked...
April 12, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29690642/autophagic-removal-of-farnesylated-carboxy-terminal-lamin-peptides
#20
Xiang Lu, Karima Djabali
The mammalian nuclear lamina proteins—prelamin A- and B-type lamins—are post-translationally modified by farnesylation, endoproteolysis, and carboxymethylation at a carboxy-terminal CAAX (C, cysteine; a, aliphatic amino acid; X, any amino acid) motif. However, prelamin A processing into mature lamin A is a unique process because it results in the production of farnesylated and carboxymethylated peptides. In cells from patients with Hutchinson⁻Gilford progeria syndrome, the mutant prelamin A protein, progerin, cannot release its prenylated carboxyl-terminal moiety and therefore remains permanently associated with the nuclear envelope (NE), causing severe nuclear alterations and a dysmorphic morphology...
April 23, 2018: Cells
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