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Nuclear lamin

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https://www.readbyqxmd.com/read/29317431/suppression-of-activated-foxo-transcription-factors-in-the-heart-prolongs-survival-in-a-mouse-model-of-laminopathies
#1
Gaelle Auguste, Priyatansh Gurha, Raffaella Lombardi, Cristian Coarfa, James T Willerson, Ali J Marian
Rationale: Mutations in the LMNA gene, encoding nuclear inner membrane protein Lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are the common causes of death in laminopathies. Objective: To identify and therapeutically target the responsible mechanism(s) for cardiac phenotype in laminopathies. Methods and Results: Whole heart RNA sequencing was performed prior to the onset of cardiac dysfunction in the Lmna-/- and matched control mice...
January 9, 2018: Circulation Research
https://www.readbyqxmd.com/read/29311549/lamin-a-c-augments-th1-differentiation-and-response-against-vaccinia-virus-and-leishmania-major
#2
Raquel Toribio-Fernández, Virginia Zorita, Vera Rocha-Perugini, Salvador Iborra, Gloria Martínez Del Hoyo, Raphael Chevre, Beatriz Dorado, David Sancho, Francisco Sanchez-Madrid, Vicente Andrés, Jose-Maria Gonzalez-Granado
Differentiation of naive CD4+ T-cells into functionally distinct T helper (Th) subsets is critical to immunity against pathogen infection. Little is known about the role of signals emanating from the nuclear envelope for T-cell differentiation. The nuclear envelope protein lamin A/C is induced in naive CD4+ T-cells upon antigen recognition and acts as a link between the nucleus and the plasma membrane during T-cell activation. Here we demonstrate that the absence of lamin A/C in naive T-cell reduces Th1 differentiation without affecting Th2 differentiation in vitro and in vivo...
January 8, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29306725/messages-from-the-voices-within-regulation-of-signaling-by-proteins-of-the-nuclear-lamina
#3
REVIEW
Larry Gerace, Olga Tapia
The nuclear lamina (NL) is a protein scaffold lining the nuclear envelope that consists of nuclear lamins and associated transmembrane proteins. It helps to organize the nuclear envelope, chromosomes, and the cytoplasmic cytoskeleton. The NL also has an important role in regulation of signaling, as highlighted by the wide range of human diseases caused by mutations in the genes for NL proteins with associated signaling defects. This review will consider diverse mechanisms for signaling regulation by the NL that have been uncovered recently, including interaction with signaling effectors, modulation of actin assembly and compositional alteration of the NL...
January 4, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29262292/mice-overexpressing-lamin-b1-in-oligodendrocytes-recapitulate-the-age-dependent-motor-signs-but-not-the-early-autonomic-cardiovascular-dysfunction-of-autosomal-dominant-leukodystrophy-adld
#4
Viviana Lo Martire, Sara Alvente, Stefano Bastianini, Chiara Berteotti, Cristiano Bombardi, Giovanna Calandra-Buonaura, Sabina Capellari, Gary Cohen, Pietro Cortelli, Laura Gasparini, Quasar Padiath, Alice Valli, Giovanna Zoccoli, Alessandro Silvani
Autosomal dominant leukodystrophy (ADLD) is a rare adult-onset demyelinating disease caused by overexpression of lamin B1, a nuclear lamina filament. Early autonomic dysfunction involving the cardiovascular system before progressive somatic motor dysfunction is a striking feature of most cases of ADLD. In the Plp-FLAG-LMNB1 transgenic mouse model, lamin B1 overexpression in oligodendrocytes elicits somatic motor dysfunction and neuropathology akin to ADLD. Here, we investigate whether Plp-FLAG-LMNB1 mice also develop autonomic cardiovascular dysfunctions before or after somatic motor dysfunction...
December 17, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29242553/nuclear-lamin-a-c-harnesses-the-perinuclear-apical-actin-cables-to-protect-nuclear-morphology
#5
Jeong-Ki Kim, Arghavan Louhghalam, Geonhui Lee, Benjamin W Schafer, Denis Wirtz, Dong-Hwee Kim
The distinct spatial architecture of the apical actin cables (or actin cap) facilitates rapid biophysical signaling between extracellular mechanical stimuli and intracellular responses, including nuclear shaping, cytoskeletal remodeling, and the mechanotransduction of external forces into biochemical signals. These functions are abrogated in lamin A/C-deficient mouse embryonic fibroblasts that recapitulate the defective nuclear organization of laminopathies, featuring disruption of the actin cap. However, how nuclear lamin A/C mediates the ability of the actin cap to regulate nuclear morphology remains unclear...
December 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29227210/separate-roles-for-chromatin-and-lamins-in-nuclear-mechanics
#6
Andrew D Stephens, Edward J Banigan, John F Marko
The cell nucleus houses, protects, and arranges the genome within the cell. Therefore, nuclear mechanics and morphology are important for dictating gene regulation, and these properties are perturbed in many human diseases, such as cancers and progerias. The field of nuclear mechanics has long been dominated by studies of the nuclear lamina, the intermediate filament shell residing just beneath the nuclear membrane. However, a growing body of work shows that chromatin and chromatin-related factors within the nucleus are an essential part of the mechanical response of the cell nucleus to forces...
December 11, 2017: Nucleus
https://www.readbyqxmd.com/read/29215717/nucleoskeletal-stiffness-regulates-stem-cell-migration-and-differentiation-through-lamin-a-c
#7
REVIEW
Liujing Chen, Fulin Jiang, Yini Qiao, Hong Li, Zhangming Wei, Tu Huang, Jingxiang Lan, Yue Xia, Juan Li
Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212225/the-relevance-of-prelamin-a-and-rad51-as-molecular-biomarkers-in-cervical-cancer
#8
Simona Leonardi, Marianna Buttarelli, Ilaria De Stefano, Gabriella Ferrandina, Marco Petrillo, Gabriele Babini, Giovanni Scambia, Carmela Marino, Mariateresa Mancuso, Daniela Gallo
Along with their role in the maintenance of nuclear architecture, nuclear lamins also control genomic stability, DNA damage repair, transcription, cell proliferation, differentiation and senescence. Recent reports reveal that prelamin A-processing defects play a role in cancer development by impacting on transcription of key players in the maintenance of the genome stability, including RAD51. Here, we performed a 'proof of concept' study evaluating the role of prelamin A and RAD51 expression in clinical outcome of cervical cancer patients...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210315/expression-of-lamina-proteins-lamin-and-kugelkern-suppresses-stem-cell-proliferation
#9
Roman Petrovsky, Jörg Großhans
The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of Lam or Kuk strongly suppressed proliferation...
December 6, 2017: Nucleus
https://www.readbyqxmd.com/read/29203402/lamin-a-expression-in-circulating-osteoprogenitors-as-a-potential-biomarker-for-frailty-the-nepean-osteoporosis-and-frailty-nof-study
#10
Ahmed Al Saedi, Piumali Gunawardene, Sandra Bermeo, Sara Vogrin, Derek Boersma, Steven Phu, Lakshman Singh, Pushpa Suriyaarachchi, Gustavo Duque
Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study...
December 1, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29196813/sense-encoded-poly-gr-dipeptide-repeat-proteins-correlate-to-neurodegeneration-and-uniquely-co-localize-with-tdp-43-in-dendrites-of-repeat-expanded-c9orf72-amyotrophic-lateral-sclerosis
#11
Shahram Saberi, Jennifer E Stauffer, Jie Jiang, Sandra Diaz Garcia, Amy E Taylor, Derek Schulte, Takuya Ohkubo, Cheyenne L Schloffman, Marcus Maldonado, Michael Baughn, Maria J Rodriguez, Don Pizzo, Don Cleveland, John Ravits
Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models...
December 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29196611/cell-signaling-abnormalities-in-cardiomyopathy-caused-by-lamin-a-c-gene-mutations
#12
REVIEW
Howard J Worman
Mutations in the lamin A/C gene (LMNA) encoding intermediate filament proteins associated with the inner nuclear membrane cause diseases known as laminopathies. Most LMNA mutations cause dilated cardiomyopathy with variable skeletal muscular dystrophy. Cell signaling abnormalities have been discovered in hearts of mouse models of cardiomyopathy caused by LMNA mutations that contribute to pathogenesis. These include abnormally increased signaling by extracellular signal-regulated kinase 1 and kinase 2 and other mitogen-activated protein kinases, protein kinase B/mammalian target of rapamycin complex 1 and transforming growth factor-β...
December 1, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29192166/spindle-associated-membrane-protein-1-samp1-is-required-for-the-differentiation-of-muscle-cells
#13
Mohammed Hakim Jafferali, Ricardo A Figueroa, Mehedi Hasan, Einar Hallberg
Muscles are developed and regenerated in a differentiation process called myogenesis, which involves components of the nuclear envelope. We have investigated Samp1 (Spindle Associated Membrane Protein 1), a transmembrane nuclear envelope protein, which interacts with emerin and lamin A, both of which are linked to Emery-Dreifuss muscular dystrophy (EDMD). We found that the levels of Samp1 increased seven-fold during differentiation of mouse C2C12 muscle progenitor cells. To test if Samp1 could have a role in myogenesis we developed stable C2C12 knockdown cell lines expressing short hairpin RNA targeting Samp1 expression...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175975/lamin-and-the-heart
#14
REVIEW
Gabriella Captur, Eloisa Arbustini, Gisèle Bonne, Petros Syrris, Kevin Mills, Karim Wahbi, Saidi A Mohiddin, William J McKenna, Stephen Pettit, Carolyn Y Ho, Antoine Muchir, Paul Gissen, Perry M Elliott, James C Moon
Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM...
November 25, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29175376/control-of-nuclear-%C3%AE-dystroglycan-content-is-crucial-for-the-maintenance-of-nuclear-envelope-integrity-and-function
#15
Griselda Vélez-Aguilera, Juan de Dios Gómez-López, Guadalupe E Jiménez-Gutiérrez, Alejandra Vásquez-Limeta, Marco S Laredo-Cisneros, Pablo Gómez, Steve J Winder, Bulmaro Cisneros
β-dystroglycan (β-DG) is a plasma membrane protein that has ability to target to the nuclear envelope (NE) to maintain nuclear architecture. Nevertheless, mechanisms controlling β-DG nuclear localization and the physiological consequences of a failure of trafficking are largely unknown. We show that β-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its transmembrane domain, by CRM1. Remarkably, NES mutations forced β-DG nuclear accumulation resulting in mislocalization and decreased levels of emerin and lamin B1 and disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and β-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are critically involved...
November 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29149836/are-there-different-kinds-of-aging
#16
Amalia Gabriela Diaconeasa
A critical analysis of the accelerated aging syndromes may explain what aging is, but also why some tissues and organs age at accelerated rates in comparison with aging rates of other tissues. Syndromes of accelerated aging are caused by mutations affecting the integrity of the genetic material. Among them, the most studied is Werner's syndrome, "adult progeria", caused by a recessive autosomal mutation with a frequency of 1 in 10 millions, which affects a helicase involved in DNA repair. In Werner syndrome, there is a loss of heterochromatin, though the stability of heterochromatin is also affected in "normal" aging...
November 16, 2017: Current Aging Science
https://www.readbyqxmd.com/read/29146355/gelatinized-wheat-starch-influences-crystallization-behaviour-and-structure-of-roll-in-shortenings-in-laminated-bakery-products
#17
Kristin D Mattice, Alejandro G Marangoni
One hydrogenated and one non-hydrogenated shortening were baked with isolated components of a croissant matrix, including crystalline wheat starch, gelatinized wheat starch, gluten, and formed gluten network. The impact of the matrix components on fat crystallization was analyzed for polymorphism using powder X-ray diffraction, solid fat content by pulsed nuclear magnetic resonance and thermal behaviour by differential scanning calorimetry. When compared to results obtained from croissants prepared with the respective shortenings, samples containing gelatinized wheat starch displayed notably similar results: polymorphic conversion, from the β' to β form over storage, and visually broader peaks in the melting endotherms indicating a greater temperature was required to completely melt all of the fat...
March 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29142071/chromatin-histone-modifications-and-rigidity-affect-nuclear-morphology-independent-of-lamins
#18
Andrew D Stephens, Patrick Z Liu, Edward J Banigan, Luay M Almassalha, Vadim Backman, Stephen A Adam, Robert D Goldman, John F Marko
Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed "blebs" are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29134302/nuclear-organization-during-in-vitro-differentiation-of-porcine-mesenchymal-stem-cells-mscs-into-adipocytes
#19
Joanna Stachecka, Agnieszka Walczak, Beata Kociucka, Błażej Ruszczycki, Grzegorz Wilczyński, Izabela Szczerbal
Differentiation of progenitor cells into adipocytes is accompanied by remarkable changes in cell morphology, cytoskeletal organization, and gene expression profile. Mature adipocytes are filled with a large lipid droplet and the nucleus tends to move to the cell periphery. It was hypothesized that the differentiation process is also associated with changes of nuclear organization. The aim of this study was to determine the number and distribution of selected components of nuclear architecture during porcine in vitro adipogenesis...
November 13, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29128844/a-biodegradable-scaffold-enhances-differentiation-of-embryonic-stem-cells-into-a-thick-sheet-of-retinal-cells
#20
Deepti Singh, Shao-Bin Wang, Tina Xia, Laurel Tainsh, Maryam Ghiassi-Nejad, Tao Xu, Shaomin Peng, Ron A Adelman, Lawrence J Rizzolo
Retinal degeneration is a leading cause of blindness in developed countries. Stem cells can be differentiated into retinal organoids to study mechanisms of retinal degeneration, develop therapeutic agents, and potentially serve as replacement tissues. The spherical nature of these retinoids limits their utility, because the investigator lacks ready access to both sides of the neo-tissue. For tissue-replacement, spherical retinoids are unable to interact simultaneously with the host retinal pigment epithelium and remaining neurosensory retina...
October 31, 2017: Biomaterials
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