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Pesquisa : D12.776.660.650.875 [Categoria DeCS]
Referências encontradas : 1273 [refinar]
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  1 / 1273 MEDLINE  
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[PMID]:29378184
[Au] Autor:Setijono SR; Park M; Kim G; Kim Y; Cho KW; Song SJ
[Ad] Endereço:Soonchunhyang Institute of Medi-Bioscience (SIMS), Soonchunhyang University, 25 Bongjeong-ro Dongnam-gu, Chungcheongnam-do, 31151, South Korea.
[Ti] Título:miR-218 and miR-129 regulate breast cancer progression by targeting Lamins.
[So] Source:Biochem Biophys Res Commun;496(3):826-833, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Breast cancer is the most frequently diagnosed life-threatening cancer in women. Triple-negative breast cancer (TNBC) has an aggressive clinical behavior, but the treatment of TNBC remains challenging. MicroRNAs (miRNAs) have emerged as a potential target for the diagnosis, therapy and prognosis of breast cancer. However, the precise role of miRNAs and their targets in breast cancer remain to be elucidated. Here we show that miR-218 is downregulated and miR-129 is upregulated in TNBC samples and their expressions confer prognosis to patients. Gain-of-function and loss-of-function analysis reveals that miR-218 has a tumor suppressive activity, while miR-129 acts as an oncomir in breast cancer. Notably, miR-218 and miR-129 directly target Lamin B1 and Lamin A, respectively, which are also found to be deregulated in human breast tumors. Finally, we demonstrate Lamins as the major factors in reliable miR-218 and miR-129 functions for breast cancer progression. Our findings uncover a new miRNA-mediated regulatory network for different Lamins and provide a potential therapeutic target for breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Regulação Neoplásica da Expressão Gênica
Laminas/metabolismo
MicroRNAs/metabolismo
[Mh] Termos MeSH secundário: Proliferação Celular
Seres Humanos
Células MCF-7
Invasividade Neoplásica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lamins); 0 (MIRN218 microRNA, human); 0 (MicroRNAs); 0 (Mirn129 microRNA, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  2 / 1273 MEDLINE  
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[PMID]:28729432
[Au] Autor:Nowak RB; Papoin J; Gokhin DS; Casu C; Rivella S; Lipton JM; Blanc L; Fowler VM
[Ad] Endereço:Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA.
[Ti] Título:Tropomodulin 1 controls erythroblast enucleation via regulation of F-actin in the enucleosome.
[So] Source:Blood;130(9):1144-1155, 2017 Aug 31.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high-resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression, and completion of mouse and human erythroblast enucleation in vivo. Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, whereas human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology. These morphological differences are linked to differential expression of Lamin isoforms, with primary mouse erythroblasts expressing only Lamin B and primary human erythroblasts only Lamin A/C. We did not consistently identify a continuous F-actin ring at the cell surface constriction in mouse erythroblasts, nor at the membrane protein-sorting boundary in human erythroblasts, which do not have a constriction, arguing against a contractile ring-based nuclear expulsion mechanism. However, both mouse and human erythroblasts contain an F-actin structure at the rear of the translocating nucleus, enriched in tropomodulin 1 (Tmod1) and nonmuscle myosin IIB. We investigated Tmod1 function in mouse and human erythroblasts both in vivo and in vitro and found that absence of Tmod1 leads to enucleation defects in mouse fetal liver erythroblasts, and in CD34 hematopoietic stem and progenitor cells, with increased F-actin in the structure at the rear of the nucleus. This novel structure, the "enucleosome," may mediate common cytoskeletal mechanisms underlying erythroblast enucleation, notwithstanding the morphological heterogeneity of enucleation across species.
[Mh] Termos MeSH primário: Actinas/metabolismo
Núcleo Celular/metabolismo
Eritroblastos/metabolismo
Tropomodulina/metabolismo
[Mh] Termos MeSH secundário: Animais
Medula Óssea/metabolismo
Diferenciação Celular
Forma do Núcleo Celular
Polaridade Celular
Feto/metabolismo
Técnicas de Silenciamento de Genes
Laminas/metabolismo
Fígado/embriologia
Camundongos Endogâmicos C57BL
Miosina não Muscular Tipo IIB/metabolismo
Isoformas de Proteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Lamins); 0 (Protein Isoforms); 0 (Tropomodulin); EC 3.6.1.- (Nonmuscle Myosin Type IIB)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-05-787051


  3 / 1273 MEDLINE  
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[PMID]:28525751
[Au] Autor:van Steensel B; Belmont AS
[Ad] Endereço:Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Department of Cell Biology, Erasmus University Medical Center, 3015 CE Rotterdam, the Netherlands. Electronic address: b.v.steensel@nki.nl.
[Ti] Título:Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression.
[So] Source:Cell;169(5):780-791, 2017 May 18.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In metazoan cell nuclei, hundreds of large chromatin domains are in close contact with the nuclear lamina. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Here, we discuss the properties of LADs, the molecular mechanisms that determine their association with the nuclear lamina, their dynamic links with other nuclear compartments, and their proposed roles in gene regulation.
[Mh] Termos MeSH primário: Núcleo Celular/química
Cromatina/química
[Mh] Termos MeSH secundário: Animais
Núcleo Celular/metabolismo
Regulação da Expressão Gênica
Heterocromatina
Seres Humanos
Laminas/metabolismo
Lâmina Nuclear/química
Poro Nuclear/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Chromatin); 0 (Heterochromatin); 0 (Lamins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170730
[Lr] Data última revisão:
170730
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE


  4 / 1273 MEDLINE  
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[PMID]:28421443
[Au] Autor:Pindyurin AV
[Ad] Endereço:Netherlands Cancer Institute, Amsterdam, 1066 CX, the Netherlands. a.pindyurin@mcb.nsc.ru.
[Ti] Título:Genomic mapping of chromatin proteins by using Dam modification of an FLP-dependent DamID approach.
[So] Source:Dokl Biochem Biophys;472(1):15-18, 2017 Jan.
[Is] ISSN:1608-3091
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:To identify interactions of chromatin proteins with the genome of the cell type of interest that is a part of heterologous tissues and organs of Drosophila, an FLP-dependent DamID approach was recently developed [4], which does not require sorting of cells or nuclei. Here, a modification of this approach, Dam , is described. The modified approach was validated by generating the binding pattern of the LAM protein, a component of the inner membrane of the nuclear envelope, with the genome of glial cells of the Drosophila larval central brains.
[Mh] Termos MeSH primário: Cromatina/genética
Mapeamento Cromossômico/métodos
Drosophila/genética
Proteínas de Escherichia coli/genética
DNA Metiltransferases Sítio Específica (Adenina-Específica)/genética
[Mh] Termos MeSH secundário: Animais
Proteínas de Drosophila/genética
Proteínas de Escherichia coli/metabolismo
Laminas/genética
Neuroglia/metabolismo
Neurônios/metabolismo
DNA Metiltransferases Sítio Específica (Adenina-Específica)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Drosophila Proteins); 0 (Escherichia coli Proteins); 0 (Lamin protein, Drosophila); 0 (Lamins); EC 2.1.1.72 (Site-Specific DNA-Methyltransferase (Adenine-Specific)); EC 2.1.1.72 (dam protein, E coli)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1134/S1607672917010057


  5 / 1273 MEDLINE  
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[PMID]:28374669
[Au] Autor:Nikolova V; Delimitreva S; Chakarova I; Zhivkova R; Hadzhinesheva V; Markova M
[Ad] Endereço:Department of Biology, Medical Faculty, Medical University of Sofia, Bulgaria.
[Ti] Título:Dynamics of Lamins B and A/C and Nucleoporin Nup160 during Meiotic Maturation in Mouse Oocytes.
[So] Source:Folia Biol (Praha);63(1):6-12, 2017.
[Is] ISSN:0015-5500
[Cp] País de publicação:Czech Republic
[La] Idioma:eng
[Ab] Resumo:This study was aimed at elucidating the fate of three important nuclear envelope components - lamins B and A/C and nucleoporin Nup160, during meiotic maturation of mouse oocytes. These proteins were localized by epifluorescence and confocal microscopy using specific antibodies in oocytes at different stages from prophase I (germinal vesicle) to metaphase II. In immature germinal vesicle oocytes, all three proteins were detected at the nuclear periphery. In metaphase I and metaphase II, lamin B co-localized with the meiotic spindle, lamin A/C was found in a diffuse halo surrounding the spindle and to a lesser degree throughout the cytoplasm, and Nup160 was concentrated to the spindle poles. To our knowledge, this is the first report on nucleoporin localization in mammalian oocytes and the first successful detection of lamins in mature oocytes. While the distribution patterns of both lamins closely paralleled the respective stages of mitosis, Nup160 localization in metaphase oocytes corresponded to that in mitotic prometaphase rather than metaphase. The peculiar distribution of this nucleoporin in oocytes may reflect its role in meiosis-specific mechanisms of spindle assembly and its regulation.
[Mh] Termos MeSH primário: Diferenciação Celular
Laminas/metabolismo
Meiose
Proteínas Nucleares/metabolismo
Oócitos/citologia
Oócitos/metabolismo
[Mh] Termos MeSH secundário: Animais
Feminino
Metáfase
Camundongos Endogâmicos BALB C
Microscopia Confocal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lamins); 0 (Nuclear Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  6 / 1273 MEDLINE  
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[PMID]:28356420
[Au] Autor:Edens LJ; Dilsaver MR; Levy DL
[Ad] Endereço:Department of Molecular Biology, University of Wyoming, Laramie, WY 82071.
[Ti] Título:PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in and mammalian cells.
[So] Source:Mol Biol Cell;28(10):1389-1399, 2017 May 15.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:How nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. We previously reported that conventional protein kinase C (cPKC) contributes to nuclear size reductions that occur during early development. Here we report that PKC-mediated phosphorylation of lamin B3 (LB3) contributes to this mechanism of nuclear size regulation. By mapping PKC phosphorylation sites on LB3 and testing the effects of phosphomutants in embryos, we identify the novel site S267 as being an important determinant of nuclear size. Furthermore, FRAP studies demonstrate that phosphorylation at this site increases lamina dynamics, providing a mechanistic explanation for how PKC activity influences nuclear size. We subsequently map this LB3 phosphorylation site to a conserved site in mammalian lamin A (LA), S268. Manipulating PKC activity in cultured mammalian cells alters nuclear size, as does expression of LA-S268 phosphomutants. Taken together, these data demonstrate that PKC-mediated lamin phosphorylation is a conserved mechanism of nuclear size regulation.
[Mh] Termos MeSH primário: Tamanho do Núcleo Celular/fisiologia
Lâmina Nuclear/metabolismo
Proteína Quinase C/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Linhagem Celular
Núcleo Celular/metabolismo
Núcleo Celular/fisiologia
Filamentos Intermediários/metabolismo
Interfase/fisiologia
Lamina Tipo A/metabolismo
Lamina Tipo B/metabolismo
Laminas/metabolismo
Mamíferos/metabolismo
Proteínas Nucleares/metabolismo
Fosforilação
Proteína Quinase C/fisiologia
Serina/metabolismo
Xenopus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lamin Type A); 0 (Lamin Type B); 0 (Lamins); 0 (Nuclear Proteins); 0 (lamin B2); 452VLY9402 (Serine); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E16-11-0786


  7 / 1273 MEDLINE  
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[PMID]:28241138
[Au] Autor:Turgay Y; Eibauer M; Goldman AE; Shimi T; Khayat M; Ben-Harush K; Dubrovsky-Gaupp A; Sapra KT; Goldman RD; Medalia O
[Ad] Endereço:Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
[Ti] Título:The molecular architecture of lamins in somatic cells.
[So] Source:Nature;543(7644):261-264, 2017 03 09.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin. Besides providing structural stability to the nucleus, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication. However, the structural organization of the nuclear lamina is poorly understood. Here we use cryo-electron tomography to obtain a detailed view of the organization of the lamin meshwork within the lamina. Data analysis of individual lamin filaments resolves a globular-decorated fibre appearance and shows that A- and B-type lamins assemble into tetrameric filaments of 3.5 nm thickness. Thus, lamins exhibit a structure that is remarkably different from the other canonical cytoskeletal elements. Our findings define the architecture of the nuclear lamin meshworks at molecular resolution, providing insights into their role in scaffolding the nuclear lamina.
[Mh] Termos MeSH primário: Laminas/química
Laminas/ultraestrutura
Lâmina Nuclear/química
Lâmina Nuclear/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Cromatina/química
Cromatina/genética
Cromatina/metabolismo
Cromatina/ultraestrutura
Microscopia Crioeletrônica
Citoesqueleto/química
Citoesqueleto/metabolismo
Citoesqueleto/ultraestrutura
Seres Humanos
Proteínas de Filamentos Intermediários/química
Proteínas de Filamentos Intermediários/metabolismo
Proteínas de Filamentos Intermediários/ultraestrutura
Laminas/metabolismo
Camundongos
Lâmina Nuclear/metabolismo
Tomografia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (Intermediate Filament Proteins); 0 (Lamins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.1038/nature21382


  8 / 1273 MEDLINE  
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[PMID]:27974395
[Au] Autor:Charar C; Gruenbaum Y
[Ad] Endereço:Department of Genetics, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel chayki18@gmail.com gru@vms.huji.ac.il.
[Ti] Título:Lamins and metabolism.
[So] Source:Clin Sci (Lond);131(2):105-111, 2017 Jan 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo: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. Mutations in lamins are also associated with the metabolic syndrome (MS). Cells derived from patients suffering from metabolic laminopathies, as well as cells derived from the corresponding animal models, show a disruption of the mechanistic target of rapamycin (mTOR) pathway, abnormal autophagy, altered proliferative rate and down-regulation of genes that regulate adipogenesis. In addition, treating Hutchinson-Gilford progeria syndrome (HGPS) cells with the mTOR inhibitor rapamycin improves their fate. In this review, we will discuss the ways by which lamin genes are involved in the regulation of cell metabolism.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Doenças Genéticas Inatas/metabolismo
Laminas/metabolismo
Doenças Metabólicas/metabolismo
[Mh] Termos MeSH secundário: Envelhecimento/genética
Animais
Doenças Genéticas Inatas/genética
Seres Humanos
Laminas/genética
Doenças Metabólicas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Lamins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


  9 / 1273 MEDLINE  
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[PMID]:26946072
[Au] Autor:Rowan S; Chang ML; Reznikov N; Taylor A
[Ad] Endereço:Tufts University JM-USDA Human Nutrition Research Center on Aging, Laboratory of Nutrition and Vision Research, 711 Washington Street Boston, MA, 02111, USA. Electronic address: sheldon.rowan@tufts.edu.
[Ti] Título:Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.
[So] Source:Exp Eye Res;156:72-78, 2017 Mar.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The eye lens is unique among tissues: it is transparent, does not form tumors, and the majority of its cells degrade their organelles, including their cell nuclei. A mystery for over a century, there has been considerable recent progress in elucidating mechanisms of lens fiber cell denucleation (LFCD). In contrast to the disassembly and reassembly of the cell nucleus during mitosis, LFCD is a unidirectional process that culminates in destruction of the fiber cell nucleus. Whereas p27 , the cyclin-dependent kinase inhibitor, is upregulated during formation of LFC in the outermost cortex, in the inner cortex, in the nascent organelle free zone, p27 is degraded, markedly activating cyclin-dependent kinase 1 (Cdk1). This process results in phosphorylation of nuclear Lamins, dissociation of the nuclear membrane, and entry of lysosomes that liberate DNaseIIß (DLAD) to cleave chromatin. Multiple cellular pathways, including the ubiquitin proteasome system and the unfolded protein response, converge on post-translational regulation of p27 . Mutations that impair these pathways are associated with congenital cataracts and loss of LFCD. These findings highlight new regulatory nodes in the lens and suggest that we are close to understanding this fascinating terminal differentiation process. Such knowledge may offer a new means to confront proliferative diseases including cancer.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Inibidor de Quinase Dependente de Ciclina p27/metabolismo
Cristalino/fisiologia
Resposta a Proteínas não Dobradas/fisiologia
[Mh] Termos MeSH secundário: Animais
Proteína Quinase CDC2/metabolismo
Catarata/congênito
Catarata/enzimologia
Catarata/patologia
Seres Humanos
Laminas/metabolismo
Cristalino/citologia
Cristalino/enzimologia
Mitose
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Lamins); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 2.7.11.22 (CDC2 Protein Kinase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170721
[Lr] Data última revisão:
170721
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160307
[St] Status:MEDLINE


  10 / 1273 MEDLINE  
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[PMID]:27798680
[Au] Autor:Noble JW; Hunter DV; Roskelley CD; Chan EK; Mills J
[Ad] Endereço:Department of Biology, Trinity Western University, Langley, British Columbia, Canada.
[Ti] Título:Loukoumasomes Are Distinct Subcellular Structures from Rods and Rings and Are Structurally Associated with MAP2 and the Nuclear Envelope in Retinal Cells.
[So] Source:PLoS One;11(10):e0165162, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:"Rods and rings" (RR) and loukoumasomes are similarly shaped, subcellular macromolecular structures with as yet unknown function. RR, so named because of their shape, are formed in response to inhibition in the GTP or CTP synthetic pathways and are highly enriched in the two key enzymes of the nucleotide synthetic pathway. Loukoumasomes also occur as linear and toroidal bodies and were initially inferred to be the same as RR, largely due to their shared shape and size and the fact that it was unclear if they shared the same subcomponents. In human retinoblastoma tissue and cells we have observed toroidal, perinuclear, macromolecular structures of similar size and antigenicity to those previously reported in neurons (neuronal-loukoumasomes). To further characterize the subcomponents of the retinal-loukoumasomes, confocal analysis following immunocytochemical staining for alpha-tubulin, beta-III tubulin and detyrosinated tubulin was performed. These studies indicate that retinal-loukoumasomes are enriched for beta-III tubulin and other tubulins associated with microtubules. Immunofluorescence together with the in situ proximity ligation assay (PLA), confirmed that beta-III tubulin colocalized with detyrosinated tubulin within loukoumasomes. Our results indicate that these tissues contain only loukoumasomes because these macromolecular structures are immunoreactive with an anti-tubulin antibody but are not recognized by the prototype anti-RR/inosine monophosphate dehydrogenase (IMPDH) antibody (It2006). To further compare the RR and retinal-loukoumasomes, retinoblastoma cells were exposed to the IMPDH-inhibitor ribavirin, a drug known to induce the formation of RR. In contrast to RR, the production of retinal-loukoumasomes was unaffected. Coimmunostaining of Y79 cells for beta-III tubulin and IMPDH indicate that these cells, when treated with ribavirin, can contain both retinal-loukoumasomes and RR and that these structures are antigenically distinct. Subcellular fractionation studies indicate that ribavirin increased the RR subcomponent, IMPDH, in the nuclear fraction of Y79 cells from 21.3 ± 5.8% (0 mM ribavirin) to 122.8 ± 7.9% (1 mM ribavirin) while the subcellular localization of the retinal-loukoumasome subcomponent tubulin went unaltered. Further characterization of retinal-loukoumasomes in retinoblastoma cells reveals that they are intimately associated with lamin folds within the nuclear envelope. Using immunofluorescence and the in situ PLA in this cell type, we have observed colocalization of beta-III tubulin with MAP2. As MAP2 is a microtubule-associated protein implicated in microtubule crosslinking, this supports a role for microtubule crosslinkers in the formation of retinal-loukoumasomes. Together, these results suggest that loukoumasomes and RR are distinct subcellular macromolecular structures, formed by different cellular processes and that there are other loukoumasome-like structures within retinal tissues and cells.
[Mh] Termos MeSH primário: Estruturas Citoplasmáticas/metabolismo
Proteínas Associadas aos Microtúbulos/metabolismo
Microtúbulos/metabolismo
Membrana Nuclear/metabolismo
Retina/citologia
Retina/metabolismo
[Mh] Termos MeSH secundário: Neurônios Adrenérgicos/metabolismo
Animais
Linhagem Celular Tumoral
Seres Humanos
Imuno-Histoquímica
Laminas/metabolismo
Ligação Proteica
Transporte Proteico
Ratos
Retinoblastoma/metabolismo
Ribavirina/farmacologia
Tubulina (Proteína)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lamins); 0 (MAP2 protein, human); 0 (Microtubule-Associated Proteins); 0 (Tubulin); 49717AWG6K (Ribavirin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0165162



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