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Glycine receptor

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https://www.readbyqxmd.com/read/28429370/the-role-of-charged-residues-in-independent-glycine-receptor-folding-domains-for-intermolecular-interactions-and-ion-channel-function
#1
Georg Langlhofer, Carmen Villmann
Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4, and C-terminal sequences is essential for pentameric receptor arrangements. In vitro coexpressions of GlyRα1 truncated N-domains and C- domains were able to restore ion channel function. An ionic interaction between both domains was hypothesised as the underlying mechanism...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429004/binding-site-opening-by-loop-c-shift-and-chloride-ion-pore-interaction-in-the-gabaa-receptor-model
#2
M A Michałowski, S Kraszewski, J W Mozrzymas
GABAA receptors (GABAARs) are crucial in mediating inhibition in the adult mammalian brain. Although the kinetics of this receptor has been extensively studied, the molecular picture of interactions occurring at various channel conformations remains elusive. While electrophysiology combined with mutagenesis sheds light on the role of specific residues, ultrastructural studies reveal static structures which, in the case of GABAARs, are limited to the β3 homomer. To take advantage of the newest crystal structures of cys-loop receptors, a homology model of α1β2γ2 GABAAR in the unbound closed state was built using a template of the homomeric glycine receptor in the closed state...
April 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28416115/in%C3%A2-vivo-measurement-of-glycine-receptor-turnover-and-synaptic-size-reveals-differences-between-functional-classes-of-motoneurons-in-zebrafish
#3
Dawnis M Chow, Kathryn A Zuchowski, Joseph R Fetcho
The interplay between binding and unbinding of synaptic receptor proteins at synapses plays an important role in determining receptor concentration and synaptic strength, with known links between changes in binding kinetics and synaptic plasticity. The regulation of such kinetics may subserve the specific functional requirements of neurons in intact circuits. However, the majority of studies of synaptic turnover kinetics have been performed in cultured neurons outside the context of normal circuits, and synaptic receptor turnover has not been measured at individual synaptic sites in vivo...
April 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28412251/c-myc-antagonises-the-transcriptional-activity-of-the-androgen-receptor-in-prostate-cancer-affecting-key-gene-networks
#4
Stefan J Barfeld, Alfonso Urbanucci, Harri M Itkonen, Ladan Fazli, Jessica L Hicks, Bernd Thiede, Paul S Rennie, Srinivasan Yegnasubramanian, Angelo M DeMarzo, Ian G Mills
Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa...
April 5, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28411489/kale-borack1-is-involved-in-the-plant-response-to-salt-stress-and-peronospora-brassicae-gaumann
#5
Da-Hong Li, Fu-Jia Shen, Hong-Yan Li, Wei Li
The receptor for activated C kinase 1 (RACK1) belongs to a protein subfamily containing a tryptophan-aspartic acid-domain (WD) repeat structure. Compelling evidence indicates that RACK1 can interact with many signal molecules and affect different signal transduction pathways. In this study, a kale (Brassica oleracea var. acephala f.tricolor) RACK1 gene (BoRACK1) was cloned by RT-PCR. The amino acid sequence of BoRACK1 had seven WD repeats in which there were typical GH (glycine-histidine) and WD dipeptides...
March 24, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28407709/synergistic-antitumor-effect-of-ing4-pten-double-tumor-suppressors-mediated-by-adenovirus-modified-with-rgd-on-glioma
#6
Yaodong Zhao, Jiarong Wang, Jicheng Yang, Jingcheng Miao
BACKGROUND: Gene therapy is regarded as a new and promising therapeutic modality for cancers, and adenovirus is one of the most frequently used vectors. However, because of low or absent coxsackievirus and adenovirus receptor levels on the surface of many kinds of tumor cells, the efficiency of adenovirus infection of target tumor cells may be low. Meanwhile, gene therapy by a single vector carrying two or more anti-oncogenes can improve treatment effects and reduce side effects from vectors...
April 12, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28403791/multimeric-system-of-rgd-grafted-pmma-nanoparticles-as-a-targeted-drug-delivery-system-for-paclitaxel
#7
Gibbens-Bandala Brenda Vianey, Ocampo-García Blanca Eli, Ferro-Flores Guillermina, Morales-Avila Enrique, Ancira-Cortez Alejandra, Jaimes-Aguirre Laura
BACKGROUND: Polymer-based nanoparticles as drug-delivery systems offer new therapeutic opportunities. Among them, ligand-mediated targeting, which increases selectivity and efficacy, allows controllable drug delivery. The aim of the this research was to prepare and characterize poly(methyl methacrylate) (PMMA) nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed at the sites of integrin receptor overexpression...
April 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28402725/visualization-of-pml-nuclear-import-complexes-reveals-fg-repeat-nucleoporins-at-cargo-retrieval-sites
#8
Anna Lång, Jens Eriksson, Kay Oliver Schink, Emma Lång, Pernille Blicher, Anna Połeć, Andreas Brech, Bjørn Dalhus, Stig Ove Bøe
Selective nuclear import in eukaryotic cells involves sequential interactions between nuclear import receptors and phenylalanine-glycine (FG)-repeat nucleoporins. Traditionally, binding of cargoes to import receptors is perceived as a nuclear pore complex independent event, while interactions between import complexes and nucleoporins are thought to take place at the nuclear pores. However, studies have shown that nucleoporins are mobile and not static within the nuclear pores, suggesting that they may become engaged in nuclear import prior to nuclear pore entry...
April 12, 2017: Nucleus
https://www.readbyqxmd.com/read/28402271/cyclic-rgdyc-functionalized-liposomes-for-dual-targeting-of-tumor-vasculature-and-cancer-cells-in-glioblastoma-an-in-vitro-boron-neutron-capture-therapy-study
#9
Weirong Kang, Darren Svirskis, Vijayalekshmi Sarojini, Ailsa L McGregor, Joseph Bevitt, Zimei Wu
The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a avβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400591/pathogenicity-and-transmission-of-a-swine-influenza-a-h6n6-virus
#10
Hailiang Sun, Bryan S Kaplan, Minhui Guan, Guihong Zhang, Jianqiang Ye, Li-Ping Long, Sherry Blackmon, Chun-Kai Yang, Meng-Jung Chiang, Hang Xie, Nan Zhao, Jim Cooley, David F Smith, Ming Liao, Carol Cardona, Lei Li, George Peng Wang, Richard Webby, Xiu-Feng Wan
Subtype H6 influenza A viruses (IAVs) are commonly detected in wild birds and domestic poultry and can infect humans. In 2010, a H6N6 virus emerged in southern China, and since then, it has caused sporadic infections among swine. We show that this virus binds to α2,6-linked and α2,3-linked sialic acids. Mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the virus hemagglutinin (HA) affected its receptor-binding properties. Experiments showed that the virus has limited transmissibility between ferrets through direct contact or through inhalation of infectious aerosolized droplets...
April 12, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28393186/a-novel-5-fluorouracil-resistant-human-esophageal-squamous-cell-carcinoma-cell-line-eca-109-5-fu-with-significant-drug-resistance-related-characteristics
#11
Chi Zhang, Qunfeng Ma, Yinan Shi, Xue Li, Ming Wang, Junfeng Wang, Jianlin Ge, Zhinan Chen, Ziling Wang, Hong Jiang
5-Fluorouracil (5-FU) is used for the clinical treatment of esophageal squamous cell carcinomas (ESCCs), yet it also induces chemoresistant cancer cells during treatment, which leads to the failure of the therapy. To further explore the resistance mechanism of 5-FU in ESCC, we established the 5-FU-resistant ESCC cell line Eca-109/5-FU, which was prepared by the stepwise exposure to increasing 5-FU concentrations. MTT assay and nude mouse xenograft models were used to test the drug resistance and proliferation of Eca-109 and Eca-109/5-FU cells in vitro and in vivo...
March 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28387240/the-low-binding-affinity-of-d-serine-at-the-ionotropic-glutamate-receptor-glud2-can-be-attributed-to-the-hinge-region
#12
Daniel Tapken, Thomas Bielefeldt Steffensen, Rasmus Leth, Lise Baadsgaard Kristensen, Alexander Gerbola, Michael Gajhede, Flemming Steen Jørgensen, Lars Olsen, Jette Sandholm Kastrup
Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383883/the-proton-responsiveness-in-the-extracellular-domain-of-glic-differs-in-the-presence-of-the-elic-transmembrane-domain
#13
Mona A Alqazzaz, Kerry L Price, Sarah C R Lummis
Prokaryotic homologues of Cys-loop receptors have proven to be useful in understanding their eukaryotic counterparts, but even the best studied of these, Gloeobacter ligand-gated ion channel (GLIC), is still not yet fully understood. GLIC is activated by protons with a pH50 between 5 and 6, implicating a histidine residue in its activation, but although a histidine residue (His11') in the pore-forming α-helix (M2) is known to be involved in gating, the His in the extracellular domain (ECD), His127, is not...
April 6, 2017: Biochemistry
https://www.readbyqxmd.com/read/28381493/recreational-concentrations-of-alcohol-enhance-synaptic-inhibition-of-cerebellar-unipolar-brush-cells-via-pre-and-postsynaptic-mechanisms
#14
Ben David Richardson, David James Rossi
Variation in cerebellar sensitivity to alcohol/ethanol (EtOH) is a heritable trait associated with alcohol use disorder (AUD) in humans and high EtOH consumption in rodents, but the underlying mechanisms are poorly understood. A recently identified cellular substrate of cerebellar sensitivity to EtOH: the GABAergic system of cerebellar granule cells (GCs), shows divergent responses to EtOH paralleling EtOH consumption and motor impairment phenotype. Although GCs are the dominant afferent integrator in the cerebellum, such integration is shared by unipolar brush cells (UBCs) in vestibulocerebellar lobes...
April 5, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28380364/organization-of-circadian-behavior-relies-on-glycinergic-transmission
#15
Lia Frenkel, Nara I Muraro, Andrea N Beltrán González, María S Marcora, Guillermo Bernabó, Christiane Hermann-Luibl, Juan I Romero, Charlotte Helfrich-Förster, Eduardo M Castaño, Cristina Marino-Busjle, Daniel J Calvo, M Fernanda Ceriani
The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28378791/computationally-discovered-potentiating-role-of-glycans-on-nmda-receptors
#16
Anton V Sinitskiy, Nathaniel H Stanley, David H Hackos, Jesse E Hanson, Benjamin D Sellers, Vijay S Pande
N-methyl-D-aspartate receptors (NMDARs) are glycoproteins in the brain central to learning and memory. The effects of glycosylation on the structure and dynamics of NMDARs are largely unknown. In this work, we use extensive molecular dynamics simulations of GluN1 and GluN2B ligand binding domains (LBDs) of NMDARs to investigate these effects. Our simulations predict that intra-domain interactions involving the glycan attached to residue GluN1-N440 stabilize closed-clamshell conformations of the GluN1 LBD. The glycan on GluN2B-N688 shows a similar, though weaker, effect...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28375879/glycine-metabolism-in-skeletal-muscle-implications-for-metabolic-homeostasis
#17
René Koopman, Marissa K Caldow, Daniel J Ham, Gordon S Lynch
PURPOSE OF REVIEW: The review summarizes the recent literature on the role of glycine in skeletal muscle during times of stress. RECENT FINDINGS: Supplemental glycine protects muscle mass and function under pathological conditions. In addition, mitochondrial dysfunction in skeletal muscle leads to increased cellular serine and glycine production and activation of NADPH-generating pathways and glutathione metabolism. These studies highlight how glycine availability modulates cellular homeostasis and redox status...
April 3, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28374007/contribution-of-resting-conductance-gabaa-receptor-mediated-miniature-synaptic-currents-and-neurosteroid-to-chloride-homeostasis-in-central-neurons
#18
Tushar D Yelhekar, Michael Druzin, Staffan Johansson
Maintenance of a low intraneuronal Cl(-) concentration, [Cl(-)]i, is critical for inhibition in the CNS. Here, the contribution of passive, conductive Cl(-) flux to recovery of [Cl(-)]i after a high load was analyzed in mature central neurons from rat. A novel method for quantifying the resting Cl(-) conductance, important for [Cl(-)]i recovery, was developed and the possible contribution of GABAA and glycine receptors and of ClC-2 channels to this conductance was analyzed. The hypothesis that spontaneous, action potential-independent release of GABA is important for [Cl(-)]i recovery was tested...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28365212/residues-in-the-glun1-c-terminal-domain-control-kinetics-and-pharmacology-of-glun1-glun3a-n-methyl-d-aspartate-receptors
#19
Kirstie A Cummings, Sophie Belin, Gabriela K Popescu
N-methyl-d-aspartate (NMDA) receptors assembled from GluN1 and GluN3 subunits are unique in that they form glycine-gated excitatory channels that are insensitive to glutamate and NMDA. Alternative splicing of the GluN1 subunit mRNA results in eight variants with regulated expression patterns and post-translational modifications. Here we investigate the role of residues in the GluN1 C-terminal alternatively spliced cassettes in receptor gating and modulation. We measured whole-cell currents from recombinant GluN1/GluN3A receptors expressed in HEK293 cells that differed in the sequence of their GluN1 C-terminal tail...
March 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28363413/action-of-bacopa-monnieri-to-antagonize-cisplatin-induced-emesis-in-suncus-murinus-house-musk-shrew
#20
Ihsan Ullah, Fazal Subhan, Zengbing Lu, Sze Wa Chan, John A Rudd
Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10-40 mg/kg, s.c.) and BM-ButFr (5-20 mg/kg, s...
March 12, 2017: Journal of Pharmacological Sciences
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