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https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#1
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#2
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
March 27, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28346090/identifying-inhibitors-of-the-hsp90-aha1-protein-complex-a-potential-target-to-drug-cystic-fibrosis-by-alpha-technology
#3
Verena Ihrig, Wolfgang M J Obermann
Deletion of a single phenylalanine residue at position 508 of the protein CFTR (cystic fibrosis transmembrane conductance regulator), a chloride channel in lung epithelium, is the most common cause for cystic fibrosis. As a consequence, folding of the CFTRΔF508 protein and delivery to the cell surface are compromised, resulting in degradation of the polypeptide. Accordingly, decreased surface presence of CFTRΔF508 causes impaired chloride ion conductivity and is associated with mucus accumulation, a hallmark of cystic fibrosis...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346011/various-plus-unique-viral-protein-u-as-a-plurifunctional-protein-for-hiv-1-replication
#4
Andrew Soper, Guillermo Juarez-Fernandez, Hirofumi Aso, Miyu Moriwaki, Eri Yamada, Yusuke Nakano, Yoshio Koyanagi, Kei Sato
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28345874/delivery-of-pesticides-to-plant-parasitic-nematodes-using-tobacco-mild-green-mosaic-virus-as-a-nanocarrier
#5
Paul L Chariou, Nicole F Steinmetz
Plant parasitic nematodes are a major burden to the global agricultural industry, causing a $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides to be applied, putting the environment and human health at risk. Challenges are to treat nematodes that are located deep within the soil, feeding on the roots of plants. To attack the problem at its roots, we propose the use of tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as a carrier to deliver nematicides...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345598/novel-1-4-dihydropyridines-for-l-type-calcium-channel-as-antagonists-for-cadmium-toxicity
#6
Madhu Sudhana Saddala, Ramesh Kandimalla, Pradeepkiran Jangampalli Adi, Sainath Sri Bhashyam, Usha Rani Asupatri
The present study, we design and synthesize the novel dihydropyridine derivatives, i.e., 3 (a-e) and 5 (a-e) and evaluated, anticonvulsant activity. Initially due to the lacuna of LCC, we modeled the protein through modeller 9.15v and evaluated through servers. Docking studies were performed with the synthesized compounds and resulted two best compounds, i.e., 5a, 5e showed the best binding energies. The activity of intracellular Ca(2+) measurements was performed on two cell lines: A7r5 (rat aortic smooth muscle cells) and SH-SY5Y (human neuroblastoma cells)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344592/dysbindin-deficiency-modifies-the-expression-of-gaba-neuron-and-ion-permeation-transcripts-in-the-developing-hippocampus
#7
Jennifer Larimore, Stephanie A Zlatic, Miranda Arnold, Kaela S Singleton, Rebecca Cross, Hannah Rudolph, Martha V Bruegge, Andrea Sweetman, Cecilia Garza, Eli Whisnant, Victor Faundez
The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28343377/protein-kinase-c-mediates-the-corticosterone-induced-sensitization-of-dorsal-root-ganglion-neurons-innervating-the-rat-stomach
#8
Meng Li, Lu Xue, Hong-Yan Zhu, Hongjun Wang, Xue Xu, Geping Wu, Guang-Yin Xu
Background/Aims: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia (FD). Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. Methods: DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall...
March 26, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28343102/acoustic-and-hybrid-3d-printed-electrochemical-biosensors-for-the-real-time-immunodetection-of-liver-cancer-cells-hepg2
#9
Samar Damiati, Seta Küpcü, Martin Peacock, Christoph Eilenberger, Mazin Zamzami, Ishtiaq Qadri, Hani Choudhry, Uwe B Sleytr, Bernhard Schuster
This study presents an efficient acoustic and hybrid three-dimensional (3D)-printed electrochemical biosensors for the detection of liver cancer cells. The biosensors function by recognizing the highly expressed tumor marker CD133, which is located on the surface of liver cancer cells. Detection was achieved by recrystallizing a recombinant S-layer fusion protein (rSbpA/ZZ) on the surface of the sensors. The fused ZZ-domain enables immobilization of the anti-CD133 antibody in a defined manner. These highly accessible anti-CD133 antibodies were employed as a sensing layer, thereby enabling the efficient detection of liver cancer cells (HepG2)...
March 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28343066/calcium-triggers-reversal-of-calmodulin-on-nested-anti-parallel-sites-in-the-iq-motif-of-the-neuronal-voltage-dependent-sodium-channel-nav1-2
#10
Liam Hovey, C Andrew Fowler, Ryan Mahling, Zesen Lin, Mark Stephen Miller, Dagan C Marx, Jesse B Yoder, Elaine H Kim, Kristin M Tefft, Brett C Waite, Michael D Feldkamp, Liping Yu, Madeline A Shea
Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1...
March 9, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28342889/heteromeric-complexes-of-aldo-keto-reductase-auxiliary-kv%C3%AE-subunits-akr6a-regulate-sarcolemmal-localization-of-kv1-5-in-coronary-arterial-myocytes
#11
Matthew A Nystoriak, Deqing Zhang, Ganapathy Jagatheesan, Aruni Bhatnagar
Redox-sensitive potassium channels consisting of the voltage-gated K(+) (KV) channel pore subunit KV1.5 regulate resting membrane potential and thereby contractility of vascular smooth muscle cells. Members of the KV1 family associate with cytosolic auxiliary β subunits, which are members of the aldo-keto reductase (AKR) superfamily (AKR6A subfamily). The Kvβ subunits have been proposed to regulate Kv1 gating via pyridine nucleotide cofactor binding. However, the molecular identity of KVβ subunits that associate with native KV1...
March 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28342823/evidence-that-increased-kcnj6-gene-dose-is-necessary-for-deficits-in-behavior-and-dentate-gyrus-synaptic-plasticity-in-the-ts65dn-mouse-model-of-down-syndrome
#12
Alexander M Kleschevnikov, Jessica Yu, Jeesun Kim, Larisa V Lysenko, Zheng Zhen, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). The gene-dose hypothesis argues that a change in the dose of individual genes or regulatory sequences on HSA21 is necessary for creating DS-related phenotypes, including cognitive impairment. We focused on a possible role for Kcnj6, the gene encoding Kir3.2 (Girk2) subunits of a G-protein-coupled inwardly-rectifying potassium channel. This gene resides on a segment of mouse Chromosome 16 that is present in one extra copy in the genome of the Ts65Dn mouse, a well-studied genetic model of DS...
March 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28342809/identity-and-function-of-a-cardiac-mitochondrial-small-conductance-ca-2-activated-k-channel-splice-variant
#13
Meiying Yang, Amadou K S Camara, Mohammed Aldakkak, Wai-Meng Kwok, David F Stowe
We provide evidence for location and function of a small conductance, Ca(2+)-activated K(+) (SKCa) channel isoform 3 (SK3) in mitochondria (m) of guinea pig, rat and human ventricular myocytes. SKCa agonists protected isolated hearts and mitochondria against ischemia/reperfusion (IR) injury; SKCa antagonists worsened IR injury. Intravenous infusion of a SKCa channel agonist/antagonist, respectively, in intact rats was effective in reducing/enhancing regional infarct size induced by coronary artery occlusion...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342732/hydrogen-bond-strength-in-membrane-proteins-probed-by-time-resolved-1-h-detected-solid-state-nmr-and-md-simulations
#14
João Medeiros-Silva, Shehrazade Jekhmane, Marc Baldus, Markus Weingarth
(1)H-detected solid-state NMR in combination with (1)H/(2)D exchange steps allows for the direct identification of very strong hydrogen bonds in membrane proteins. On the example of the membrane-embedded potassium channel KcsA, we quantify the longevity of such very strong hydrogen bonds by combining time-resolved (1)H-detected solid-state NMR experiments and molecular dynamics simulations. In particular, we show that the carboxyl-side chain of the highly conserved residue Glu51 is involved in ultra-strong hydrogen bonds, which are fully-water-exposed and yet stable for weeks...
March 18, 2017: Solid State Nuclear Magnetic Resonance
https://www.readbyqxmd.com/read/28342583/affinity-chromatographic-methodologies-based-on-immobilized-voltage-dependent-anion-channel-isoform-1-and-application-in-protein-ligand-interaction-analysis-and-bioactive-compounds-screening-from-traditional-medicine
#15
Qian Li, Pan Qiao, Xiu Chen, Jing Wang, Liujiao Bian, Xiaohui Zheng
Voltage dependent anion channel isoform 1 (VDAC-1) serves as an attractive target of anti-cancer drugs by mediating the entry and exit of metabolites between cytoplasm and mitochondria. This work reports on the preparation of a VDAC-1-based bioaffinity chromatographic stationary phase by linking the protein on lecithin modified microspheres. An assay of chromatographic methods including frontal analysis, zonal elution, injection dependent analysis and nonlinear chromatography were utilized to investigate the bindings of ATP, NADH and NADPH to VDAC-1...
March 18, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28342022/identifying-connexin-expression-and-determining-gap-junction-intercellular-communication-in-rainbow-trout-cells
#16
Joshua Hooper, Sarah J Poynter, Stephanie J DeWitte-Orr
Gap junctions are groups of membrane-bound channels that allow the passage of small molecules and ions between cells, permitting cell-cell communication. Because of their importance in cell homeostasis, gap junction presence and function were characterized in three commonly studied rainbow trout cell lines, namely RTgill-W1, RTgutGC, and RTG-2. Firstly, gap junction presence was determined by screening for gap junction protein alpha 7 and alpha 1 (GJA7 and GJA1) presence at the transcript level and GJA7 at the protein level...
March 24, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28341892/aquaporin-4-forms-a-macromolecular-complex-with-glutamate-transporter-1-and-mu-opioid-receptor-in-astrocytes-and-participates-in-morphine-dependence
#17
Hui Wang, Shiqi Wang, Kang Zhang, Hua Wang, Liting Lan, Xiaoyun Ma, Xiaoyan Liu, Shuzhuo Zhang, Jianquan Zheng, Xiaoli Wei, Haitao Yan
The water channel aquaporin 4 (AQP4) is abundantly expressed in astrocytes and provides a mechanism by which water permeability of the plasma membrane can be regulated. Evidence suggests that AQP4 is associated with glutamate transporter-1 (GLT-1) for glutamate clearance and contributes to morphine dependence. Previous studies show that AQP4 deficiency changed the mu opioid receptor expression and opioid receptors' characteristics as well. In this study, we focused on whether AQP4 could form macromolecular complex with GLT-1 and mu opioid receptor (MOR) and participates in morphine dependence...
March 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28341806/polar-localization-of-the-nip5-1-boric-acid-channel-is-maintained-by-endocytosis-and-facilitates-boron-transport-in-arabidopsis-roots
#18
Sheliang Wang, Akira Yoshinari, Tomoo Shimada, Ikuko Hara-Nishimura, Namiki Mitani-Ueno, Jian Feng Ma, Satoshi Naito, Junpei Takano
Boron uptake in Arabidopsis thaliana is mediated by nodulin 26-like intrinsic protein (NIP)5;1, a boric acid channel that is located preferentially on the soil side of the plasma membrane in root cells. However, the mechanism underlying this polar localization is poorly understood. Here, we show that the polar localization of NIP5;1 in epidermal and endodermal root cells is mediated by the phosphorylation of Thr residues in the conserved TPG (ThrProGly) repeat in the N-terminal region of NIP5;1. Although substitutions of Ala for three Thr residues in the TPG repeat did not affect lateral diffusion in the plasma membrane, these substitutions inhibited endocytosis and strongly compromised the polar localization of GFP-NIP5;1...
March 24, 2017: Plant Cell
https://www.readbyqxmd.com/read/28341653/locomotion-behavior-is-affected-by-the-g%C3%AE-s-pathway-and-the-two-pore-domain-k-channel-twk-7-interacting-in-gabaergic-motor-neurons-in-caenorhabditis-elegans
#19
Dieter-Christian Gottschling, Frank Döring, Kai Lüersen
Adjusting the efficiency of movement in response to environmental cues is an essential integrative characteristic of adaptive locomotion behavior across species. However, the modulatory molecules and the pathways involved are largely unknown. Recently, we demonstrated that in Caenorhabditis elegans, a loss of function of the two-pore-domain potassium (K2P) channel TWK-7 causes a fast, coordinated, persistent forward crawling behavior in which five central aspects of stimulated locomotion -- velocity, direction, wave parameters, duration and straightness -- are affected...
March 24, 2017: Genetics
https://www.readbyqxmd.com/read/28341438/engineering-a-novel-porin-ompgf-via-strand-replacement-from-computational-analysis-of-sequence-motif
#20
Meishan Lin, Ge Zhang, Monifa Fahie, Leslie K Morgan, Min Chen, Timothy A Keiderling, Linda J Kenney, Jie Liang
β -barrel membrane proteins (βMPs) form barrel-shaped pores in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Because of the robustness of their barrel structures, βMPs have great potential as nanosensors for single-molecule detection. However, natural βMPs currently employed have inflexible biophysical properties and are limited in their pore geometry, hindering their applications in sensing molecules of different sizes and properties. Computational engineering has the promise to generate βMPs with desired properties...
March 21, 2017: Biochimica et Biophysica Acta
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