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Nuclear pore complex

Ashley Boehringer, Robert Bowser
In eukaryotic cells, transcription and translation are compartmentalized by the nuclear membrane, requiring an active transport of RNA from the nucleus into the cytoplasm. This is accomplished by a variety of transport complexes that contain either a member of the exportin family of proteins and translocation fueled by GTP hydrolysis or in the case of mRNA by complexes containing the export protein NXF1. Recent evidence indicates that RNA transport is altered in a number of different neurodegenerative diseases including Huntington's disease, Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis...
2018: Advances in Neurobiology
Rachel Brough, Aditi Gulati, Syed Haider, Rahul Kumar, James Campbell, Erik Knudsen, Stephen J Pettitt, Colm J Ryan, Christopher J Lord
Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating molecular profiling data with data from multiple genetic perturbation screens, we identified candidate synthetic lethal (SL) interactions associated with RB1 defects in TNBC. We refined this analysis by identifying the highly penetrant effects, reasoning that these would be more robust in the face of molecular heterogeneity and would represent more promising therapeutic targets...
June 18, 2018: Oncogene
Shyamal Mosalaganti, Jan Kosinski, Sahradha Albert, Miroslava Schaffer, Daniela Strenkert, Patrice A Salomé, Sabeeha S Merchant, Jürgen M Plitzko, Wolfgang Baumeister, Benjamin D Engel, Martin Beck
Nuclear pore complexes (NPCs) span the nuclear envelope and mediate nucleocytoplasmic exchange. They are a hallmark of eukaryotes and deeply rooted in the evolutionary origin of cellular compartmentalization. NPCs have an elaborate architecture that has been well studied in vertebrates. Whether this architecture is unique or varies significantly in other eukaryotic kingdoms remains unknown, predominantly due to missing in situ structural data. Here, we report the architecture of the algal NPC from the early branching eukaryote Chlamydomonas reinhardtii and compare it to the human NPC...
June 18, 2018: Nature Communications
Feridun Akkafa, İsmail Koyuncu, Ebru Temiz, Hasan Dagli, Fuat Dïlmec, Halit Akbas
Lung has critic function in gas exchange, supplying oxygen to all cells. Rapid metastasis and the high rate of mortality characterises lung cancer. There are two types of this disease, small cell and non-small cell, which differs from each other according to histopathologic features. To date, many therapeutic approaches have been developed to destroy this deadly type of cancer, which one of them is mRNA targeted therapies through miRNA. miRNAs are 19-25 base paired molecules be able to suppress and destruct mRNA and found to be involved in development and progression of lung cancer...
June 12, 2018: Biochemical and Biophysical Research Communications
Maja Radulovic, Harald Stenmark
The multisubunit endosomal sorting complex required for transport (ESCRT) machinery is a key regulator of cellular membrane dynamics. Initially characterized in the budding yeast Saccharomyces cerevisiae for its involvement in cargo sorting to the vacuole, the yeast lysosome, this protein complex has emerged over the past decade as a driver for diverse membrane remodeling processes. Its pleiotropic functional connection is mirrored in numerous cellular processes, such as cytokinetic abscission during the final step of cell division, nuclear pore quality control, nuclear envelope sealing and repair, plasma membrane repair, vesicle shedding from the plasma membrane, viral budding, and axonal pruning...
June 14, 2018: Biochemical Society Transactions
Daniel H Lin, Ana R Correia, Sarah W Cai, Ferdinand M Huber, Claudia A Jette, André Hoelz
The nuclear pore complex (NPC) controls the passage of macromolecules between the nucleus and cytoplasm, but how the NPC directly participates in macromolecular transport remains poorly understood. In the final step of mRNA export, the DEAD-box helicase DDX19 is activated by the nucleoporins Gle1, Nup214, and Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures of Gle1•Nup42 from three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution of the DDX19 ATPase cycle establishes that human DDX19 activation does not require IP6 , unlike its fungal homologs, and that Gle1 stability affects DDX19 activation...
June 13, 2018: Nature Communications
Roland Remenyi, Yanni Gao, Ruth E Hughes, Alistair Curd, Carsten Zothner, Michelle Peckham, Andres Merits, Mark Harris
Chikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months or even years in patients. The non-structural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used sub-diffraction multi-color microscopy for spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate replicon RNA. Round cytoplasmic granules of various sizes (i) contained nsP3 and stress granule assembly factors 1 and 2 (G3BP1/2); (ii) were next to double-stranded RNA foci and nsP1-positive structures; and (iii) were close to the nuclear membrane and the nuclear pore complex protein Nup98...
June 6, 2018: Journal of Virology
Kundan Sengupta
The genome of higher eukaryotes is non-randomly organized in the interphase nucleus. However, notwithstanding the absence of membrane bound sub-compartments, the nucleus coordinates a number of functions largely by organizing chromatin in a non-random but dynamic manner. The plasticity of chromatin structure and function relies on epigenetic modifications as well as its association with nuclear landmarks such as the nuclear envelope, nuclear lamina, nuclear pore complex and nuclear bodies such as the nucleolus among others...
June 2018: Journal of Biosciences
Guillaume Holzer, Wolfram Antonin
Nuclear pore complexes are the transport gates to the nucleus. Most proteins forming these huge complexes are evolutionarily conserved, as is the eightfold symmetry of these complexes. A new study reporting the structure of the yeast nuclear pore complex now shows striking differences from its human counterpart.
June 4, 2018: Current Biology: CB
Claudia C Preston, Saranya P Wyles, Santiago Reyes, Emily C Storm, Bruce W Eckloff, Randolph S Faustino
BACKGROUND: Atrial fibrillation is a cardiac disease driven by numerous idiopathic etiologies. NUP155 is a nuclear pore complex protein that has been identified as a clinical driver of atrial fibrillation, yet the precise mechanism is unknown. The present study employs a systems biology algorithm to identify effects of NUP155 disruption on cardiogenicity in a model of stem cell-derived differentiation. METHODS: Embryonic stem (ES) cell lines (n = 5) with truncated NUP155 were cultured in parallel with wild type (WT) ES cells (n = 5), and then harvested for RNAseq...
May 30, 2018: BMC Systems Biology
Xun X Bao, Christos Spanos, Tomoko Kojidani, Eric M Lynch, Juri Rappsilber, Yasushi Hiraoka, Tokuko Haraguchi, Kenneth E Sawin
Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe , the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the g-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146...
May 29, 2018: ELife
Meltem Tatli, Ohad Medalia
Lamins are the main component of the nuclear lamina, a protein meshwork at the inner nuclear membrane which primarily provide mechanical stability to the nucleus. Lamins, type V intermediate filament proteins, are also involved in many nuclear activities. Structural analysis of nuclei revealed that lamins form 3.5nm thick filaments often interact with nuclear pore complexes. Mutations in the LMNA gene, encoding A-type lamins, have been associated with at least 15 distinct diseases collectively termed laminopathies, including muscle, metabolic and neurological disorders, and premature aging syndrome...
May 22, 2018: Current Opinion in Cell Biology
Guangyuan Zhao, Cheng Zheng, Cuifang Kuang, Renjie Zhou, Mohammad M Kabir, Kimani C Toussaint, Wensheng Wang, Liang Xu, Haifeng Li, Peng Xiu, Xu Liu
We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity...
May 11, 2018: Physical Review Letters
Benoit Souquet, Ellen Freed, Alessandro Berto, Vedrana Andric, Nicolas Audugé, Bernardo Reina-San-Martin, Elizabeth Lacy, Valérie Doye
Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. Studies on a null mutation in mice previously revealed that Nup133 is essential for embryonic development but not for mouse embryonic stem cell (mESC) proliferation. Using single-pore detection and average NE-fluorescence intensity, we find that Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. However, loss of Nup133 specifically perturbs the formation of the nuclear basket as manifested by the absence of Tpr in about half of the NPCs combined with altered dynamics of Nup153...
May 22, 2018: Cell Reports
Magdalena Chmielewska, Dmitry Dedukh, Katarzyna Haczkiewicz, Beata Rozenblut-Kościsty, Mikołaj Kaźmierczak, Krzysztof Kolenda, Ewa Serwa, Agnieszka Pietras-Lebioda, Alla Krasikova, Maria Ogielska
DNA elimination is a radical form of gene silencing and occurs both in somatic and germ cells. The programmed DNA elimination occurs during gametogenesis in interspecies hybrids that reproduce by hybridogenesis (stick insects, fishes, and amphibians) and concerns removal of whole genomes of one of the parental species and production of clonal gametes propagating the genome of the other species. The cellular mechanisms differ considerably in hybridogenetic insects and fishes but remains unknown in edible frogs Pelophylax esculentus, natural hybrids between Pelophylax lessonae and Pelophylax ridibundus...
May 18, 2018: Scientific Reports
So-Mi Kang, Min-Ho Yoon, Bum-Joon Park
Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy...
May 16, 2018: BMB Reports
Everton Lucas-Oliveira, Arthur G Araujo-Ferreira, Willian A Trevizan, Carlos A Fortulan, Tito J Bonagamba
Nowadays, most of the efforts in NMR applied to porous media are dedicated to studying the molecular fluid dynamics within and among the pores. These analyses have a higher complexity due to morphology and chemical composition of rocks, besides dynamic effects as restricted diffusion, diffusional coupling, and exchange processes. Since the translational nuclear spin diffusion in a confined geometry (e.g. pores and fractures) requires specific boundary conditions, the theoretical solutions are restricted to some special problems and, in many cases, computational methods are required...
May 4, 2018: Journal of Magnetic Resonance
Diana Rüthnick, Elmar Schiebel
The main microtubule organizing centre in the unicellular model organisms Saccharomyces cerevisiae and Schizosaccharomyces pompe is the spindle pole body (SPB). The SPB is a multilayer structure, which duplicates exactly once per cell cycle. Unlike higher eukaryotic cells, both yeast model organisms undergo mitosis without breakdown of the nuclear envelope (NE), a so-called closed mitosis. Therefore, in order to simultaneously nucleate nuclear and cytoplasmic MTs, it is vital to embed the SPB into the NE at least during mitosis, similarly to the nuclear pore complex (NPC)...
May 10, 2018: Cells
Masumi Okamura, Yasutaka Yamanaka, Maki Shigemoto, Yuya Kitadani, Yuhko Kobayashi, Taiho Kambe, Masaya Nagao, Issei Kobayashi, Katsuzumi Okumura, Seiji Masuda
DBP5, also known as DDX19, GLE1 and inositol hexakisphosphate (IP6) function in messenger RNA (mRNA) export at the cytoplasmic surface of the nuclear pore complex in eukaryotic cells. DBP5 is a DEAD-box RNA helicase, and its activity is stimulated by interactions with GLE1 and IP6. In addition, these three factors also have unique role(s). To investigate how these factors influenced the cytoplasmic mRNA expression and cell phenotype change, we performed RNA microarray analysis to detect the effect and function of DBP5, GLE1 and IP6 on the cytoplasmic mRNA expression...
2018: PloS One
Yichen Li, Wangxi Luo, Weidong Yang
Nuclear translocation of stimulated Smad heterocomplexes is a critical step in the signal transduction of transforming growth factor β (TGF-β) from transmembrane receptors into the nucleus. Specifically, normal nuclear accumulation of Smad2/Smad4 heterocomplexes induced by TGF-β1 is involved in carcinogenesis. However, the relationship between nuclear accumulation and the nucleocytoplasmic transport kinetics of Smad proteins in the presence of TGF-β1 remains obscure. By combining a high-speed single-molecule tracking microscopy and Förster resonance energy transfer technique, we tracked the entire TGF-β1-induced process of Smad2/Smad4 heterocomplex formation, as well as their transport through nuclear pore complexes in live cells, with a high single-molecule localization precision of 2 ms and <20 nm...
May 8, 2018: Biophysical Journal
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