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nuclear pore

Kyung-Ha Lee, Peipei Zhang, Hong Joo Kim, Diana M Mitrea, Mohona Sarkar, Brian D Freibaum, Jaclyn Cika, Maura Coughlin, James Messing, Amandine Molliex, Brian A Maxwell, Nam Chul Kim, Jamshid Temirov, Jennifer Moore, Regina-Maria Kolaitis, Timothy I Shaw, Bing Bai, Junmin Peng, Richard W Kriwacki, J Paul Taylor
Expansion of a hexanucleotide repeat GGGGCC (G4C2) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (G4C2) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles...
October 20, 2016: Cell
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
James Wilson, Leila Sloman, Zhiren He, Aleksei Aksimentiev
An inexpensive, reliable method for protein sequencing is essential to unraveling the biological mechanisms governing cellular behavior and disease. Current protein sequencing methods suffer from limitations associated with the size of proteins that can be sequenced, the time, and the cost of the sequencing procedures. Here, we report the results of all-atom molecular dynamics simulations that investigated the feasibility of using graphene nanopores for protein sequencing. We focus our study on the biologically significant phenylalanine-glycine repeat peptides (FG-nups)-parts of the nuclear pore transport machinery...
July 19, 2016: Advanced Functional Materials
Ying Zhang, Xiaoyu Guo, Juan Dong
Cell polarization is commonly used for the regulation of stem cell asymmetric division in both animals and plants. Stomatal development in Arabidopsis, a process that produces breathing pores in the epidermis, requires asymmetric cell division to differentiate highly specialized guard cells while maintaining a stem cell population [1, 2]. The BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) protein exhibits a polarized localization pattern in the cell and is required for differential cell fates resulting from asymmetric cell division [3]...
October 5, 2016: Current Biology: CB
Claudia Joseph, Jens Mibus, Paul Trepte, Christa Müller, Vinzenz Brendler, Dan M Park, Yongqin Jiao, Annie B Kersting, Mavrik Zavarin
As a contribution to the safety assessment of nuclear waste repositories, U(VI) diffusion through the potential buffer material MX-80 bentonite was investigated at three clay dry densities over six years. Synthetic MX-80 model pore water was used as background electrolyte. Speciation calculations showed that Ca2UO2(CO3)3(aq) was the main U(VI) species. The in- and out-diffusion of U(VI) was investigated separately. U(VI) diffused about 3mm, 1.5mm, and 1mm into the clay plug at ρ=1.3, 1.6, and 1.9g/cm(3), respectively...
October 11, 2016: Science of the Total Environment
Brant M Webster, David J Thaller, Jens Jäger, Sarah E Ochmann, Sapan Borah, C Patrick Lusk
The integrity of the nuclear envelope barrier relies on membrane remodeling by the ESCRTs, which seal nuclear envelope holes and contribute to the quality control of nuclear pore complexes (NPCs); whether these processes are mechanistically related remains poorly defined. Here, we show that the ESCRT-II/III chimera, Chm7, is recruited to a nuclear envelope subdomain that expands upon inhibition of NPC assembly and is required for the formation of the storage of improperly assembled NPCs (SINC) compartment. Recruitment to sites of NPC assembly is mediated by its ESCRT-II domain and the LAP2-emerin-MAN1 (LEM) family of integral inner nuclear membrane proteins, Heh1 and Heh2...
October 12, 2016: EMBO Journal
Thai V Hoang, Caroline Kizilyaprak, Danièle Spehner, Bruno M Humbel, Patrick Schultz
Focused Ion Beam milling combined with Scanning Electron Microscopy is a powerful tool to determine the 3-D organization of whole cells and tissue at an isotropic resolution of 3-5nm. This opens the possibility to quantify several cellular parameters and to provide detailed phenotypic information in normal or disease states. Here we describe Biocomputing methods to extract in an automated way characteristic features of mouse rod photoreceptor nuclei such as the shape and the volume of the nucleus; the proportion of heterochromatin; the number, density and distribution of nuclear pore complexes (NPC)...
October 8, 2016: Journal of Structural Biology
Xudong Chen, Yue Wang, Yu-Zen Chen, Brian L Harry, Akihisa Nakagawa, Eui-Seung Lee, Hongyan Guo, Ding Xue
Caspases are cysteine proteases with critical roles in apoptosis. The Caenorhabditis elegans caspase CED-3 is activated by autocatalytic cleavage, a process enhanced by CED-4. Here we report that the CED-3 zymogen localizes to the perinuclear region in C. elegans germ cells and that CED-3 autocatalytic cleavage is held in check by C. elegans nuclei and activated by CED-4. The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro...
October 10, 2016: Nature Structural & Molecular Biology
Pei Zhang, Owen E Branson, Michael A Freitas, Mark R Parthun
BACKGROUND: There are 11 variants of linker histone H1 in mammalian cells. Beyond their shared abilities to stabilize and condense chromatin, the H1 variants have been found to have non-redundant functions, the mechanisms of which are not fully understood. Like core histones, there are both replication-dependent and replication-independent linker histone variants. The histone chaperones and other factors that regulate linker histone dynamics in the cell are largely unknown. In particular, it is not known whether replication-dependent and replication-independent linker histones interact with distinct or common sets of proteins...
October 1, 2016: BMC Biochemistry
Alberto Garcia, Jose F Rodriguez Matas, Manuela T Raimondi
Recent evidence suggests that mechanical deformation of the cell nucleus regulates the nuclear import of the transcriptional activators of genes involved in primary physiological cell responses such as stem cell differentiation. In addition, this nuclear mechanosensing response is de-regulated in pathological states, such as cancer and neurodegeneration. One hypothesis that could greatly advance the field is that the deformation of the nuclear envelope activates nuclear pore complexes through a direct mechanical link...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Benjamin L Timney, Barak Raveh, Roxana Mironska, Jill M Trivedi, Seung Joong Kim, Daniel Russel, Susan R Wente, Andrej Sali, Michael P Rout
Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability...
October 10, 2016: Journal of Cell Biology
Yang Li, Lei Wang, Bo Li, Meicheng Zhang, Rui Wen, Xinghua Guo, Xing Li, Ji Zhang, Shoujian Li, Lijian Ma
A new strategy combining pore-free matrix and cooperative-chelating was proposed in the present paper in order to effectively avoid undesired non-selective physical adsorption and intra-particle diffusion caused by pores and voids in porous sorbents, and to greatly enhance uranium-chelating capability based on hyperbranched amidoxime ligands on the surface of nanodiamond particles. Thus a pore-free, amidoxime-terminated hyperbranched nanodiamond (ND-AO) was designed and synthesized. The experimental results demonstrate that the strategy endows the as-synthesized ND-AO with following expected features: (1) distinctively high uranium selectivity (SU = qe-U /qe-tol ×100 %) from over 80% to nearly 100 % over the whole weak acidity range (pH < 4...
October 4, 2016: ACS Applied Materials & Interfaces
Netta Vidavsky, Anat Akiva, Ifat Kaplan-Ashiri, Katya Rechav, Lia Addadi, Steve Weiner, Andreas Schertel
Many important biological questions can be addressed by studying in 3D large volumes of intact, cryo fixed hydrated tissues (⩾10,000μm(3)) at high resolution (5-20nm). This can be achieved using serial FIB milling and block face surface imaging under cryo conditions. Here we demonstrate the unique potential of the cryo-FIB-SEM approach using two extensively studied model systems; sea urchin embryos and the tail fin of zebrafish larvae. We focus in particular on the environment of mineral deposition sites...
September 28, 2016: Journal of Structural Biology
Ravikiran S Yedidi, Amatullah K Fatehi, Cordula Enenkel
The ubiquitin-proteasome system (UPS) plays a critical role in cellular protein homeostasis and is required for the turnover of short-lived and unwanted proteins, which are targeted by poly-ubiquitination for degradation. Proteasome is the key protease of UPS and consists of multiple subunits, which are organized into a catalytic core particle (CP) and a regulatory particle (RP). In Saccharomyces cerevisiae, proteasome holo-enzymes are engaged in degrading poly-ubiquitinated substrates and are mostly localized in the nucleus during cell proliferation...
September 28, 2016: Critical Reviews in Biochemistry and Molecular Biology
Carus H Y Lau, Glenn F King, Mehdi Mobli
Voltage-sensor domains (VSDs) are modular transmembrane domains of voltage-gated ion channels that respond to changes in membrane potential by undergoing conformational changes that are coupled to gating of the ion-conducting pore. Most spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state. To understand the molecular basis underlying this mode of action, we used nuclear magnetic resonance to delineate the atomic details of the interaction between the VSD of the voltage-gated potassium channel KvAP and the spider-venom peptide VSTx1...
September 28, 2016: Scientific Reports
Taehyun Ryu, Melissa Bonner, Irene Chiolo
Repairing double-strand breaks (DSBs) is particularly challenging in heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. In Drosophila cells, faithful homologous recombination (HR) repair of heterochromatic DSBs relies on a specialized pathway that relocalizes repair sites to the nuclear periphery before Rad51 recruitment. Here we show that HR progression is initially blocked inside the heterochromatin domain by SUMOylation and the coordinated activity of two distinct Nse2 SUMO E3 ligases: Quijote (Qjt) and Cervantes (Cerv)...
September 27, 2016: Nucleus
Christina Li, Alexander Goryaynov, Weidong Yang
The nuclear pore complex (NPC) mediates the shuttle transport of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The permeability barrier formed by intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups) in the NPC functions as the critical selective control for nucleocytoplasmic transport. Signal-independent small molecules (< 40 kDa) passively diffuse through the pore, but passage of large cargo molecules is inhibited unless they are chaperoned by nuclear transport receptors (NTRs)...
September 27, 2016: Nucleus
Sommayya Aftab, Jaida Manzoor, Nabila Talat, Hafiz Sajid Khan, Maroof Subhanie, Nauman Abbas Khalid
Allgrove syndrome or triple-Asyndrome is a rare familial multisystem autosomal recessive disorder. It is characterised by triad of alacrima, achalasia and adrenal insufficiency due to adrenocorticotropin hormone (ACTH) resistance. If it is associated with autonomic dysfunction, it is termed as 4-Asyndrome. This syndrome is caused by a mutation in the Achalasia - Addisonism - Alacrima (AAAS) gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. A5-year boy presented with history of fits and altered sensorium for one day...
September 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Liliane Christ, Camilla Raiborg, Eva M Wenzel, Coen Campsteijn, Harald Stenmark
The endosomal sorting complex required for transport (ESCRT) machinery is an assembly of protein subcomplexes (ESCRT I-III) that cooperate with the ATPase VPS4 to mediate scission of membrane necks from the inside. The ESCRT machinery has evolved as a multipurpose toolbox for mediating receptor sorting, membrane remodeling, and membrane scission, with ESCRT-III as the major membrane-remodeling component. Cellular membrane scission processes mediated by ESCRT-III include biogenesis of multivesicular endosomes, budding of enveloped viruses, cytokinetic abscission, neuron pruning, plasma membrane wound repair, nuclear pore quality control, nuclear envelope reformation, and nuclear envelope repair...
September 23, 2016: Trends in Biochemical Sciences
José María Mateos, Bruno Guhl, Jana Doehner, Gery Barmettler, Andres Kaech, Urs Ziegler
Fluorescence microscopy reveals molecular expression at nanometer resolution but lacks ultrastructural context information. This deficit often hinders a clear interpretation of results. Electron microscopy provides this contextual subcellular detail, but protein identification can often be problematic. Correlative light and electron microscopy produces complimentary information that expands our knowledge of protein expression in cells and tissue. Inherent methodological difficulties are however encountered when combining these two very different microscopy technologies...
September 26, 2016: Scientific Reports
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