Abstract：
:The GGGGCC (G4C2) repeat expansion mutation in the C9ORF72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Transcription of the repeat and formation of nuclear RNA foci, which sequester specific RNA-binding proteins, is one of the possible pathological mechanisms. Here, we show that (G4C2) n repeat RNA predominantly associates with essential paraspeckle proteins SFPQ, NONO, RBM14, FUS and hnRNPH and colocalizes with known paraspeckle-associated RNA hLinc-p21. As formation of paraspeckles in motor neurons has been associated with early phases of ALS, we investigated the extent of similarity between paraspeckles and (G4C2) n RNA foci. Overexpression of (G4C2)72 RNA results in their increased number and colocalization with SFPQ-stained nuclear bodies. These paraspeckle-like (G4C2)72 RNA foci form independently of the known paraspeckle scaffold, the long non-coding RNA NEAT1 Moreover, the knockdown of SFPQ protein in C9ORF72 expansion mutation-positive fibroblasts significantly reduces the number of (G4C2) n RNA foci. In conclusion, (G4C2) n RNA foci have characteristics of paraspeckles, which suggests that both RNA foci and paraspeckles play roles in FTD and ALS, and implies approaches for regulation of their formation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Bajc Česnik A,Darovic S,Prpar Mihevc S,Štalekar M,Malnar M,Motaln H,Lee YB,Mazej J,Pohleven J,Grosch M,Modic M,Fonovič M,Turk B,Drukker M,Shaw CE,Rogelj Bdoi
10.1242/jcs.224303subject
Has Abstractpub_date
2019-03-07 00:00:00issue
5eissn
0021-9533issn
1477-9137pii
jcs.224303journal_volume
132pub_type
杂志文章abstract：:Macroautophagy is a dynamic process whereby portions of the cytosol are encapsulated in double-membrane vesicles and delivered to the lysosome for degradation. Phosphatidylinositol-3-phosphate (PtdIns3P) is concentrated on autophagic vesicles and recruits effector proteins that are crucial for this process. The produc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.080341
更新日期：2011-03-01 00:00:00
abstract：:We investigated human Hap50, the large isoform of the previously characterized Hsp70/Hsc70-associating protein Hap46, also called BAG-1, for effects on transcriptional activities. Overproduction by transient transfection led to enhanced expression of reporter gene constructs in various cell types using different promo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.243238
更新日期：2020-12-07 00:00:00
abstract：:Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.084152
更新日期：2012-06-15 00:00:00
abstract：:The expression of the brush border-associated hydrolase sucrase-isomaltase was shown to increase from early to late passages of Caco-2 cells, concomitant with a decrease in the rates of glucose consumption. Twenty-six clones were isolated from early (P29) and late (P198) passages of the cell line. These clones show co...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Nuclear actin plays an important role in many processes that regulate gene expression. Cytoplasmic actin dynamics are tightly controlled by numerous actin-binding proteins, but regulation of nuclear actin has remained unclear. Here, we performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to ident...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.169441
更新日期：2015-07-01 00:00:00
abstract：:An analysis of the concanavalinA binding polypeptide components of bovine tongue epithelial desmosomes reveals that in addition to the known desmosomal glycoproteins of 100/115K (the 'desmocollins'), 140K and 160/165K ('desmoglein 1') there is an uncharacterized glycoprotein of 125K (K = Mr x 10(-3). This latter polyp...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for no...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.240077
更新日期：2020-05-14 00:00:00
abstract：:Insulin-like growth factor-1 (IGF-1) has been shown to induce skeletal muscle hypertrophy, to prevent the loss of muscle mass with ageing and to improve the muscle phenotype of dystrophic mice. We previously developed a model of IGF-1-induced hypertrophy of human myotubes, in which hypertrophy was not only characteriz...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03371
更新日期：2007-02-15 00:00:00
abstract：:Although many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.137604
更新日期：2014-02-01 00:00:00
abstract：:Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.113233
更新日期：2014-05-01 00:00:00
abstract：:We have studied caveolin-1 expression and the frequency and distribution of typical invaginated caveolae as they are identified by electron microscopy in the polarized epithelial cell lines MDCK II and Caco-2. In wild-type MDCK II cells caveolin expression is high and more than 400 caveolae/mm filter were observed at ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Cell-free extracts of Xenopus eggs support nuclear assembly and DNA replication in vitro. Extracts supplemented with the protein phosphatase inhibitor microcystin-LR displayed various inhibitory effects at different concentrations of the toxin. In the presence of cycloheximide, additions of microcystin did not induce ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Rab proteins comprise a family of monomeric GTPases that control cellular membrane traffic. Rab21 is a poorly characterised member with no known function. Human Rab21 cDNA from K562 cells was subcloned into GFP expression vectors to generate Rab21 and Rab21 mutants defective in either GTP hydrolysis (Rab21 Q78L) or bi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01560
更新日期：2004-12-15 00:00:00
abstract：:Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.03306
更新日期：2007-01-01 00:00:00
abstract：:Changes in the cytoskeletal structure of cultured A10 smooth muscle cells induced by calyculin-A (CL-A), a potent inhibitor of types 1 and 2A protein phosphatases, were analyzed using indirect fluorescence techniques. In the presence of 1 x 10(-7) M CL-A the cells became round and subsequently detached from the substr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Integrins mediate cell adhesion and signal transduction at focal adhesions. Here we investigate the roles of integrin beta subunits in the regulation of actin cytoskeletal structure and the activities of Rho and Rac. The overexpression of beta3 integrin in Chinese hamster ovary cells enhances Rho activity and stress f...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-05-15 00:00:00
abstract：:We report here an analysis of the execution point of the temperature-sensitive Saccharomyces cerevisiae cell cycle mutant, cdc27-47. When a logarithmically growing culture was shifted from standard growth conditions (strain 27.8B growing in YEPD at 25 degrees C) to the restrictive temperature cell division ceased abru...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Myofibroblasts, characterised by high expression of alpha-smooth muscle actin (alpha-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:By passing a suspension of polymorphonuclear leucocytes through a parallel-plate chamber their adhesiveness can be assessed by scoring the number of cells trapped on the lower plate, and the fluid shear stress can be defined for a given flow rate. Since the adhesiveness of the cell at the instant of collision must exc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Plectin, a cytolinker protein greater than 500 kDa in size, has an important role as a mechanical stabiliser of cells. It interlinks the various cytoskeletal filament systems and anchors intermediate filaments to peripheral junctional complexes. In addition, there is increasing evidence that plectin acts as a scaffold...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02891
更新日期：2006-05-01 00:00:00
abstract：:Increasing evidence indicates that cellular uptake of several molecules can occur independently of functional dynamin, but the molecular players that regulate dynamin-independent endocytosis and the subsequent trafficking steps are still largely unknown. A survival-based short-hairpin (sh) RNA screen using a cell line...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.071712
更新日期：2010-12-15 00:00:00
abstract：:Nutritive tubes, the microtubule-based translocation channels that link the trophic tissue to the developing oocytes in the ovaries of hemipteran insects, have been isolated and examined using video-enhanced differential interference contrast microscopy. When viewed in this way the nutritive tubes are seen to fray int...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Structures retaining many of the morphological features of nuclei may be released by gently lysing human cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids contain superhelical DNA. Using a double-labelling procedure we have compared, at different salt concentrations, t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:The proteasome is the major degradation machinery of the cell that regulates multiple cellular processes as diverse as cell cycle, signal transduction and gene expression. Recognition and unfolding of target proteins involves the regulatory cap whose base contains six AAA-ATPases that display reverse chaperone activit...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02743
更新日期：2006-01-15 00:00:00
abstract：:Little is known about the molecular mechanisms that regulate the organization of vascular lumen. In this paper we show that lumen formation correlates with endothelial polarization. Adherens junctions (AJs) and VE-cadherin (VEC, encoded by CDH5) are required for endothelial apicobasal polarity in vitro and during embr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.059329
更新日期：2010-04-01 00:00:00
abstract：:The ryanodine receptor (RyR) is an ion channel composed of four identical subunits mediating calcium efflux from the endo/sarcoplasmic reticulum of excitable and non-excitable cells. We present several lines of evidence indicating that the RyR2 N-terminus is capable of self-association. A combination of yeast two-hybr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.133538
更新日期：2013-11-01 00:00:00
abstract：:Neuronal morphology plays an essential role in neuronal function. The establishment and maintenance of neuronal morphology is intimately linked to the actin cytoskeleton; however, the molecular mechanisms that regulate changes in neuronal morphology are poorly understood. Here we identify a novel myosin-Va (MyoVa)-int...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.050344
更新日期：2009-10-15 00:00:00
abstract：:Notwithstanding the fact that adult bone marrow cell engraftment to epithelial organs seems a somewhat uncommon event, there is no doubt it does occur, and under appropriate conditions of a strong and positive selection pressure these cells will expand clonally and make a significant contribution to tissue replacement...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00269
更新日期：2003-02-15 00:00:00
abstract：:Organelle transport is vital for the development and maintenance of axons, in which the distances between sites of organelle biogenesis, function, and recycling or degradation can be vast. Movement of mitochondria in axons can serve as a general model for how all organelles move: mitochondria are easy to identify, the...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.02745
更新日期：2005-12-01 00:00:00
