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Nuclear lamin

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https://www.readbyqxmd.com/read/28102353/cofilin-regulates-nuclear-architecture-through-a-myosin-ii-dependent-mechanotransduction-module
#1
O'Neil Wiggan, Bryce Schroder, Diego Krapf, James R Bamburg, Jennifer G DeLuca
Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#2
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28088180/nuclear-envelope-structural-proteins-facilitate-nuclear-shape-changes-accompanying-embryonic-differentiation-and-fidelity-of-gene-expression
#3
Elizabeth R Smith, Yue Meng, Robert Moore, Jeffrey D Tse, Arn G Xu, Xiang-Xi Xu
BACKGROUND: Nuclear size and shape are specific to a cell type, function, and location, and can serve as indicators of disease and development. We previously found that lamin A/C and associated nuclear envelope structural proteins were upregulated when murine embryonic stem (ES) cells differentiated to primitive endoderm cells. Here we further investigated the morphological changes of nuclei that accompany this differentiation. RESULTS: The nuclei of undifferentiated wild type cells were found shaped as flattened, irregular ovals, whereas nuclei of Gata4-positive endoderm cells were more spherical, less flattened, and with a slightly reduced volume...
January 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28057760/chromatin-and-lamin-a-determine-two-different-mechanical-response-regimes-of-the-cell-nucleus
#4
Andrew D Stephens, Edward J Banigan, Stephen A Adam, Robert D Goldman, John F Marko
The cell nucleus must continually resist and respond to inter- and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics are associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here, we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei...
January 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28056360/nuclear-envelope-localization-of-lemd2-is-developmentally-dynamic-and-lamin-a-c-dependent-yet-insufficient-for-heterochromatin-tethering
#5
Katharina Thanisch, Congdi Song, Dieter Engelkamp, Jeannette Koch, Audrey Wang, Einar Hallberg, Roland Foisner, Heinrich Leonhardt, Colin L Stewart, Boris Joffe, Irina Solovei
Peripheral heterochromatin in mammalian nuclei is tethered to the nuclear envelope by at least two mechanisms here referred to as the A- and B-tethers. The A-tether includes lamins A/C and additional unknown components presumably INM protein(s) interacting with both lamins A/C and chromatin. The B-tether includes the inner nuclear membrane (INM) protein Lamin B-receptor, which binds B-type lamins and chromatin. Generally, at least one of the tethers is always present in the nuclear envelope of mammalian cells...
January 2, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28053025/activity-dependent-dynamics-of-the-transcription-factor-of-camp-response-element-binding-protein-in-cortical-neurons-revealed-by-single-molecule-imaging
#6
Hironobu Kitagawa, Noriyuki Sugo, Masatoshi Morimatsu, Yoshiyuki Arai, Toshio Yanagida, Nobuhiko Yamamoto
: Transcriptional regulation is crucial for neuronal activity-dependent processes that govern neuronal circuit formation and synaptic plasticity. An intriguing question is how neuronal activity influences the spatiotemporal interactions between transcription factors and their target sites. Here, using a single-molecule imaging technique, we investigated the activity dependence of DNA binding and dissociation events of cAMP-response element binding protein (CREB), a principal factor in activity-dependent transcription, in mouse cortical neurons...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28050601/progeroid-syndrome-patients-with-zmpste24-deficiency-could-benefit-when-treated-with-rapamycin-and-dimethylsulfoxide
#7
Baris Akinci, Shireesha Sankella, Christopher Gilpin, Keiichi Ozono, Abhimanyu Garg, Anil K Agarwal
Patients with progeroid syndromes such as mandibuloacral dysplasia, type B (MADB) and restrictive dermopathy (RD) harbor mutations in zinc metalloproteinase (ZMPSTE24), an enzyme essential for posttranslational proteolysis of prelamin A to form mature lamin A. Dermal fibroblasts from these patients show increased nuclear dysmorphology and reduced proliferation; however, the efficacy of various pharmacological agents in reversing these cellular phenotypes remains unknown. In this study, fibroblasts from MADB patients exhibited marked nuclear abnormalities and reduced proliferation that improved upon treatment with rapamycin and dimethylsulfoxide but not with other agents, including farnesyl transferase inhibitors...
January 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28046052/integrative-analysis-of-immunological-data-to-explore-chronic-immune-t-cell-activation-in-successfully-treated-hiv-patients
#8
Marie-Quitterie Picat, Isabelle Pellegrin, Juliette Bitard, Linda Wittkop, Cécile Proust-Lima, Benoît Liquet, Jean-François Moreau, Fabrice Bonnet, Patrick Blanco, Rodolphe Thiébaut
OBJECTIVES: To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. DESIGN: Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. METHODS: Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years...
2017: PloS One
https://www.readbyqxmd.com/read/28045568/tissue-specific-nets-alter-genome-organization-and-regulation-even-in-a-heterologous-system
#9
Jose I de Las Heras, Nikolaj Zuleger, Dzmitry G Batrakou, Rafal Czapiewski, Alastair R W Kerr, Eric C Schirmer
Different cell types exhibit distinct patterns of 3D genome organization that correlate with changes in gene expression in tissue and differentiation systems. Several tissue-specific nuclear envelope transmembrane proteins (NETs) have been found to influence the spatial positioning of genes and chromosomes that normally occurs during tissue differentiation. Here we study 3 such NETs: NET29, NET39, and NET47, which are expressed preferentially in fat, muscle and liver, respectively. We found that even when exogenously expressed in a heterologous system they can specify particular genome organization patterns and alter gene expression...
January 3, 2017: Nucleus
https://www.readbyqxmd.com/read/28043971/mechanosensing-by-the-nucleus-from-pathways-to-scaling-relationships
#10
REVIEW
Sangkyun Cho, Jerome Irianto, Dennis E Discher
The nucleus is linked mechanically to the extracellular matrix via multiple polymers that transmit forces to the nuclear envelope and into the nuclear interior. Here, we review some of the emerging mechanisms of nuclear mechanosensing, which range from changes in protein conformation and transcription factor localization to chromosome reorganization and membrane dilation up to rupture. Nuclear mechanosensing encompasses biophysically complex pathways that often converge on the main structural proteins of the nucleus, the lamins...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28031328/interactome-analysis-reveals-a-novel-role-for-rad6-in-the-regulation-of-proteasome-activity-and-localization-in-response-to-dna-damage
#11
Hongli An, Lu Yang, Chen Wang, Zhixue Gan, Haihui Gu, Tao Zhang, Xin Huang, Yan Liu, Yufeng Li, Shing-Jyh Chang, Jianghua Lai, Ya-Bin Li, Su Chen, Fang-Lin Sun
RAD6, an E2 ubiquitin-conjugating enzyme, is a key node for determining different DNA damage repair pathways, controlling both the "error-prone" and "error-free" DNA damage repair pathways through differentially regulating the ubiquitination of the proliferating cell nuclear antigen (PCNA) protein. However, whether other pathways are involved in the RAD6-mediated regulation of DNA damage repair is still unclear. To deeply understand the molecular mechanisms of RAD6 in DNA damage repair, we performed a proteomic analysis and identified the changes of the protein-protein interaction (PPI) networks of RAD6 before and after X-ray irradiation...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28012437/autophagy-deficient-keratinocytes-display-increased-dna-damage-senescence-and-aberrant-lipid-composition-after-oxidative-stress-in-vitro-and-in-vivo
#12
Xiuzu Song, Marie Sophie Narzt, Ionela Mariana Nagelreiter, Philipp Hohensinner, Lucia Terlecki-Zaniewicz, Erwin Tschachler, Johannes Grillari, Florian Gruber
Autophagy allows cells fundamental adaptations to metabolic needs and to stress. Using autophagic bulk degradation cells can clear crosslinked macromolecules and damaged organelles that arise under redox stress. Accumulation of such debris results in cellular dysfunction and is observed in aged tissue and senescent cells. Conversely, promising anti-aging strategies aim at inhibiting the mTOR pathway and thereby activating autophagy, to counteract aging associated damage. We have inactivated autophagy related 7 (Atg7), an essential autophagy gene, in murine keratinocytes (KC) and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28002813/sub-lethal-oxidative-stress-induces-lysosome-biogenesis-via-a-lysosomal-membrane-permeabilization-cathepsin-caspase-3-transcription-factor-eb-dependent-pathway
#13
San Min Leow, Shu Xian Serene Chua, Gireedhar Venkatachalam, Liang Shen, Le Luo, Marie-Veronique Clement
Here we provide evidence to link sub-lethal oxidative stress to lysosomal biogenesis. Exposure of cells to sub-lethal concentrations of exogenously added hydrogen peroxide resulted in cytosol to nuclear translocation of the Transcription Factor EB (TFEB), the master controller of lysosome biogenesis and function. Nuclear translocation of TFEB was dependent upon the activation of a cathepsin-caspase 3 signaling pathway, downstream of a lysosomal membrane permeabilization and accompanied by a significant increase in lysosome numbers as well as induction of TFEB dependent lysosome-associated genes expression such as Ctsl, Lamp2 and its spliced variant Lamp2a, Neu1and Ctsb and Sqstm1 and Atg9b...
December 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994771/a-novel-role-of-lamins-from-genetic-disease-to-cancer-biomarkers
#14
REVIEW
Kunnathur Murugesan Sakthivel, Poonam Sehgal
Lamins are the key components of the nuclear lamina and by virtue of their interactions with chromatin and binding partners act as regulators of cell proliferation and differentiation. Of late, the diverse roles of lamins in cellular processes have made them the topic of intense debate for their role in cancer progression. The observations about aberrant localization or misexpression of the nuclear lamins in cancerous tissues have often led to the speculative role of lamins as a cancer risk biomarker. Here we discuss the involvement of lamins in several cancer subtypes and their potential role in predicting the tumor progression...
October 10, 2016: Oncology Reviews
https://www.readbyqxmd.com/read/27974395/lamins-and-metabolism
#15
REVIEW
Chayki Charar, Yosef Gruenbaum
Lamins are nuclear intermediate filaments (IFs) with important roles in most nuclear activities, including nuclear organization and cell-cycle progression. Mutations in human lamins cause over 17 different diseases, termed laminopathies. Most of these diseases are autosomal dominant and can be roughly divided into four major groups: muscle diseases, peripheral neuronal diseases, accelerated aging disorders and metabolic diseases including Dunnigan type familial partial lipodystrophy (FLPD), acquired partial lipodystrophy (APL) and autosomal dominant leucodystrophy...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27929926/comparing-lamin-proteins-post-translational-relative-stability-using-a-2a-peptide-based-system-reveals-elevated-resistance-of-progerin-to-cellular-degradation
#16
Di Wu, Phillip A Yates, Haoyue Zhang, Kan Cao
Nuclear lamins are the major components of the nuclear lamina at the periphery of the nucleus, supporting the nuclear envelope and participating in many nuclear processes, including DNA replication, transcription and chromatin organization. A group of diseases, the laminopathies, is associated with mutations in lamin genes. One of the most striking cases is Hutchinson-Gilford progeria syndrome (HGPS) which is the consequence of a lamin A dominant negative mutant named progerin. Due to the abnormal presence of a permanent C-terminal farnesyl tail, progerin gradually accumulates on the nuclear membrane, perturbing a diversity of signalings and transcriptional events...
November 2016: Nucleus
https://www.readbyqxmd.com/read/27911330/fhl1b-interacts-with-lamin-a-c-and%C3%A2-emerin-at-the-nuclear-lamina-and%C3%A2-is%C3%A2-misregulated-in-emery-dreifuss-muscular-dystrophy
#17
Esma Ziat, Kamel Mamchaoui, Maud Beuvin, Isabelle Nelson, Feriel Azibani, Simone Spuler, Gisèle Bonne, Anne T Bertrand
BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is associated with mutations in EMD and LMNA genes, encoding for the nuclear envelope proteins emerin and lamin A/C, indicating that EDMD is a nuclear envelope disease. We recently reported mutations in FHL1 gene in X-linked EDMD. FHL1 encodes FHL1A, and the two minor isoforms FHL1B and FHL1C. So far, none have been described at the nuclear envelope. OBJECTIVE: To gain insight into the pathophysiology of EDMD, we focused our attention on the poorly characterized FHL1B isoform...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27901466/differentiation-alters-stem-cell-nuclear-architecture-mechanics-and-mechano-sensitivity
#18
Su-Jin Heo, Tristan P Driscoll, Stephen D Thorpe, Nandan L Nerurkar, Brendon M Baker, Michael T Yang, Christopher S Chen, David A Lee, Robert L Mauck
Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation-induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical-loading-induced calcium signaling and differentiated marker expression...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27883036/the-mevalonate-pathway-regulates-primitive-streak-formation-via-protein-farnesylation
#19
Yoshimi Okamoto-Uchida, Ruoxing Yu, Norio Miyamura, Norie Arima, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Suguru Yoshida, Takamitsu Hosoya, Makiko Nawa, Takeshi Kasama, Yoichi Asaoka, Reiner Wimmer Alois, Ulrich Elling, Josef M Penninger, Sachiko Nishina, Noriyuki Azuma, Hiroshi Nishina
The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875985/nuclear-envelope-structural-defect-underlies-the-main-cause-of-aneuploidy-in-ovarian-carcinogenesis
#20
Callinice D Capo-Chichi, Toni M Yeasky, Elizabeth R Smith, Xiang-Xi Xu
BACKGROUND: The Cancer Atlas project has shown that p53 is the only commonly (96 %) mutated gene found in high-grade serous epithelial ovarian cancer, the major histological subtype. Another general genetic change is extensive aneuploidy caused by chromosomal numerical instability, which is thought to promote malignant transformation. Conventionally, aneuploidy is thought to be the result of mitotic errors and chromosomal nondisjunction during mitosis. Previously, we found that ovarian cancer cells often lost or reduced nuclear lamina proteins lamin A/C, and suppression of lamin A/C in cultured ovarian epithelial cells leads to aneuploidy...
November 22, 2016: BMC Cell Biology
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