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LINC complex

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https://www.readbyqxmd.com/read/29051223/crispr-cas9-based-screening-of-long-noncoding-rnas-lncrnas-in-macrophages-with-an-nf-kappa-b-reporter
#1
Sergio Covarrubias, Elektra K Robinson, Barbara Shapleigh, Apple Vollmers, Solomon Katzman, Nicole Hanley, Nicholas Fong, Michael T McManus, Susan Carpenter
The innate immune system protects against infections by initiating an inducible inflammatory response. NF-kappa B (NF-KB) is one of the critical transcription factors controlling this complex response, but some aspects of its regulation remain unclear. For example, although long noncoding RNAs (lncRNAs) have been shown to critically regulate gene expression, only a fraction of these have been functionally characterized, and the extent to which lncRNAs control NF-KB expression is unknown. Here, we describe the generation of a GFP-based NF-KB reporter system in immortalized murine bone marrow-derived macrophages (iBMDMs)...
October 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29040414/luma-is-not-essential-for-murine-cardiac-development-and-function
#2
Matthew John Stroud, Xi Fang, Jianlin Zhang, Nuno Guimarães-Camboa, Jennifer Veevers, Nancy D Dalton, Yusu Gu, William H Bradford, Kirk L Peterson, Sylvia M Evans, Larry Gerace, Ju Chen
Aims: Luma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart that is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm, and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in LUMA is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy...
October 12, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29021110/collaborative-care-from-the-emergency-department-for-injured-patients-with-prescription-drug-misuse-an-open-feasibility-study
#3
Lauren K Whiteside, Doyanne Darnell, Karlee Jackson, Jin Wang, Joan Russo, Dennis M Donovan, Douglas F Zatzick
Collaborative Care is a comprehensive longitudinal care management strategy. The purpose of this pilot effectiveness-implementation hybrid study was to determine the feasibility of a Collaborative Care intervention initiated from the Emergency Department and proceeding longitudinally for six months for injured patients with prescription drug misuse (PDM). Adult patients presenting to an urban ED with an injury were screened for eligibility from 2/2015-8/2015. Eligible participants with a positive screen for PDM were enrolled in the 'ED-LINC' intervention which included the following elements: 1) active care coordination and linkage, 2) medication safety and utilization of opioid guidelines 3) longitudinal care management and 4) utilization of Electronic Medical Record (EMR) innovations such as the statewide Emergency Department Information Exchange (EDIE) and statewide prescription monitoring program information for assessment and follow-up...
November 2017: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/28988861/centrifugal-displacement-of-nuclei-reveals-multiple-linc-complex-mechanisms-for-homeostatic-nuclear-positioning
#4
Ruijun Zhu, Susumu Antoku, Gregg G Gundersen
Nuclear movement is critical for developmental events, cell polarity, and migration and is usually mediated by linker of nucleoskeleton and cytoskeleton (LINC) complexes connecting the nucleus to cytoskeletal elements. Compared to active nuclear movement, relatively little is known about homeostatic positioning of nuclei, including whether it is an active process. To explore homeostatic nuclear positioning, we developed a method to displace nuclei in adherent cells using centrifugal force. Nuclei displaced by centrifugation rapidly recentered by mechanisms that depended on cell context...
October 23, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28973463/paragsea-a-scalable-approach-for-large-scale-gene-expression-profiling
#5
Shaoliang Peng, Shunyun Yang, Xiaochen Bo, Fei Li
More studies have been conducted using gene expression similarity to identify functional connections among genes, diseases and drugs. Gene Set Enrichment Analysis (GSEA) is a powerful analytical method for interpreting gene expression data. However, due to its enormous computational overhead in the estimation of significance level step and multiple hypothesis testing step, the computation scalability and efficiency are poor on large-scale datasets. We proposed paraGSEA for efficient large-scale transcriptome data analysis...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28854936/nuclear-envelopathies-a-complex-linc-between-nuclear-envelope-and-pathology
#6
REVIEW
Alexandre Janin, Delphine Bauer, Francesca Ratti, Gilles Millat, Alexandre Méjat
Since the identification of the first disease causing mutation in the gene coding for emerin, a transmembrane protein of the inner nuclear membrane, hundreds of mutations and variants have been found in genes encoding for nuclear envelope components. These proteins can be part of the inner nuclear membrane (INM), such as emerin or SUN proteins, outer nuclear membrane (ONM), such as Nesprins, or the nuclear lamina, such as lamins A and C. However, they physically interact with each other to insure the nuclear envelope integrity and mediate the interactions of the nuclear envelope with both the genome, on the inner side, and the cytoskeleton, on the outer side...
August 30, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28831067/the-function-of-the-inner-nuclear-envelope-protein-sun1-in-mrna-export-is-regulated-by-phosphorylation
#7
Ping Li, Maria Stumpf, Rolf Müller, Ludwig Eichinger, Gernot Glöckner, Angelika A Noegel
SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801801/nuclear-envelope-a-new-frontier-in-plant-mechanosensing
#8
REVIEW
Kateryna Fal, Atef Asnacios, Marie-Edith Chabouté, Olivier Hamant
In animals, it is now well established that forces applied at the cell surface are propagated through the cytoskeleton to the nucleus, leading to deformations of the nuclear structure and, potentially, to modification of gene expression. Consistently, altered nuclear mechanics has been related to many genetic disorders, such as muscular dystrophy, cardiomyopathy and progeria. In plants, the integration of mechanical signals in cell and developmental biology has also made great progress. Yet, while the link between cell wall stresses and cytoskeleton is consolidated, such cortical mechanical cues have not been integrated with the nucleoskeleton...
August 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28747499/effects-of-inner-nuclear-membrane-proteins-sun1-unc-84a-and-sun2-unc-84b-on-the-early-steps-of-hiv-1-infection
#9
Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H Malim
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#10
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose E Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28716842/outer-nuclear-membrane-protein-kuduk-modulates-the-linc-complex-and-nuclear-envelope-architecture
#11
Zhao-Ying Ding, Ying-Hsuan Wang, Yu-Cheng Huang, Myong-Chol Lee, Min-Jen Tseng, Ya-Hui Chi, Min-Lang Huang
Linker of nucleoskeleton and cytoskeleton (LINC) complexes spanning the nuclear envelope (NE) contribute to nucleocytoskeletal force transduction. A few NE proteins have been found to regulate the LINC complex. In this study, we identify one, Kuduk (Kud), which can reside at the outer nuclear membrane and is required for the development of Drosophila melanogaster ovarian follicles and NE morphology of myonuclei. Kud associates with LINC complex components in an evolutionarily conserved manner. Loss of Kud increases the level but impairs functioning of the LINC complex...
September 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28678660/the-functionally-elusive-rabi-chromosome-configuration-directly-regulates-nuclear-membrane-remodeling-at-mitotic-onset
#12
Alfonso Fernández-Álvarez, Julia Promisel Cooper
Despite its ubiquity in interphase eukaryotic nuclei, the functional significance of the RabI configuration, in which interphase centromeres are clustered at the nuclear envelope (NE) near the centrosome and telomeres localize at the opposite end of the nucleus, has remained mysterious. In a broad variety of organisms, including Schizosaccharomyces pombe, the RabI configuration is maintained throughout mitotic interphase. The fission yeast linker of nucleoskeleton and cytoskeleton (LINC) complex mediates this centromere association...
August 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#13
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28625779/multiple-isoforms-of-nesprin1-are-integral-components-of-ciliary-rootlets
#14
Chloe Potter, Wanqiu Zhu, David Razafsky, Philip Ruzycki, Alexander V Kolesnikov, Teresa Doggett, Vladimir J Kefalov, Ewelina Betleja, Moe R Mahjoub, Didier Hodzic
SYNE1 (synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (nuclear envelope spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (Figure 1A) [1-4]. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [5-7], a family of transmembrane proteins of the inner nuclear membrane (INM) [8, 9], to form the so-called LINC complexes (linkers of the nucleoskeleton and cytoskeleton) that span the entire NE and mediate nuclear positioning [10-12]...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28586283/mkl1-dependent-gene-activation-is-sufficient-to-induce-actin-cap-assembly
#15
Ketan Thakar, Christopher W Carroll
Actin-dependent forces mechanically control both the position and shape of the nucleus. While the mechanisms that establish nuclear position are well defined, less understood is how actin filaments determine nuclear shape. We recently showed that nuclear envelope-spanning LINC complexes promote stress fiber assembly by activating the small GTPase RhoA and Mkl1-dependent gene activation. We now report that a subset of these stress fibers associate with the apical face of the nuclear envelope through LINC complexes that contain the inner nuclear membrane protein Sun2...
June 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28580009/the-emerging-role-of-the-cytoskeleton-in-chromosome-dynamics
#16
REVIEW
Maya Spichal, Emmanuelle Fabre
Chromosomes underlie a dynamic organization that fulfills functional roles in processes like transcription, DNA repair, nuclear envelope stability, and cell division. Chromosome dynamics depend on chromosome structure and cannot freely diffuse. Furthermore, chromosomes interact closely with their surrounding nuclear environment, which further constrains chromosome dynamics. Recently, several studies enlighten that cytoskeletal proteins regulate dynamic chromosome organization. Cytoskeletal polymers that include actin filaments, microtubules and intermediate filaments can connect to the nuclear envelope via Linker of the Nucleoskeleton and Cytoskeleton (LINC) complexes and transfer forces onto chromosomes inside the nucleus...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28533284/nesprin-1%C3%AE-2-is-essential-for-mouse-postnatal-viability-and-nuclear-positioning-in-skeletal-muscle
#17
Matthew J Stroud, Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, Ju Chen
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28493118/position-matters-multiple-functions-of-linc-dependent-chromosome-positioning-during-meiosis
#18
Kazuhiro Katsumata, Eriko Nishi, Sadia Afrin, Kaoru Narusawa, Ayumu Yamamoto
Chromosome positioning is crucial for multiple chromosomal events, including DNA replication, repair, and recombination. The linker of nucleoskeleton and cytoskeleton (LINC) complexes, which consist of conserved nuclear membrane proteins, were shown to control chromosome positioning and facilitate various biological processes by interacting with the cytoskeleton. However, the precise functions and regulation of LINC-dependent chromosome positioning are not fully understood. During meiosis, the LINC complexes induce clustering of telomeres, forming the bouquet chromosome arrangement, which promotes homologous chromosome pairing...
December 2017: Current Genetics
https://www.readbyqxmd.com/read/28455503/lamins-and-nesprin-1-mediate-inside-out-mechanical-coupling-in-muscle-cell-precursors-through-fhod1
#19
Christine Schwartz, Martina Fischer, Kamel Mamchaoui, Anne Bigot, Thevy Lok, Claude Verdier, Alain Duperray, Richard Michel, Ian Holt, Thomas Voit, Suzanna Quijano-Roy, Gisèle Bonne, Catherine Coirault
LINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448008/a-protocol-for-using-f%C3%A3-rster-resonance-energy-transfer-fret-force-biosensors-to-measure-mechanical-forces-across-the-nuclear-linc-complex
#20
Paul T Arsenovic, Kranthidhar Bathula, Daniel E Conway
The LINC complex has been hypothesized to be the critical structure that mediates the transfer of mechanical forces from the cytoskeleton to the nucleus. Nesprin-2G is a key component of the LINC complex that connects the actin cytoskeleton to membrane proteins (SUN domain proteins) in the perinuclear space. These membrane proteins connect to lamins inside the nucleus. Recently, a Förster Resonance Energy Transfer (FRET)-force probe was cloned into mini-Nesprin-2G (Nesprin-TS (tension sensor)) and used to measure tension across Nesprin-2G in live NIH3T3 fibroblasts...
April 11, 2017: Journal of Visualized Experiments: JoVE
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