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https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#1
Xin Xu, Lucas Pozzo-Miller
Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Deletion of Mecp2 in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects "Hebbian" long-term synaptic plasticity. Since the excitatory/inhibitory (E/I) balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses...
June 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28611207/adult-ventricular-myocytes-segregate-kcnq1-and-kcne1-to-keep-the-iks-amplitude-in-check-until-when-larger-iks-is-needed
#2
Min Jiang, Yuhong Wang, Gea-Ny Tseng
BACKGROUND: KCNQ1 and KCNE1 assemble to form the slow delayed rectifier (IKs) channel critical for shortening ventricular action potentials during high β-adrenergic tone. However, too much IKs under basal conditions poses an arrhythmogenic risk. Our objective is to understand how adult ventricular myocytes regulate the IKs amplitudes under basal conditions and in response to stress. METHODS AND RESULTS: We express fluorescently tagged KCNQ1 and KCNE1 in adult ventricular myocytes and follow their biogenesis and trafficking paths...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28607619/molecular-mechanisms-underlying-the-pilsicainide-induced-stabilization-of-herg-proteins-in-transfected-mammalian-cells
#3
Takeshi Onohara, Ichiro Hisatome, Yasutaka Kurata, Peili Li, Tomomi Notsu, Kumi Morikawa, Naoyuki Otani, Akio Yoshida, Kazuhiko Iitsuka, Masaru Kato, Junichiro Miake, Haruaki Ninomiya, Katsumi Higaki, Yasuaki Shirayoshi, Takashi Nishihara, Toshiyuki Itoh, Yoshinobu Nakamura, Motonobu Nishimura
BACKGROUND: Pilsicainide, classified as a relatively selective Na(+) channel blocker, also has an inhibitory action on the rapidly-activating delayed-rectifier K(+) current (IKr ) through human ether-a-go-go-related gene (hERG) channels. We studied the effects of chronic exposure to pilsicainide on the expression of wild-type (WT) hERG proteins and WT-hERG channel currents, as well as on the expression of mutant hERG proteins, in a heterologous expression system. METHODS: HEK293 cells stably expressing WT or mutant hERG proteins were subjected to Western blotting, immunofluorescence microscopy and patch-clamp experiments...
June 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28601983/functions-of-intrinsic-disorder-in-transmembrane-proteins
#4
REVIEW
Magnus Kjaergaard, Birthe B Kragelund
Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine receptors...
June 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28597987/trafficking-and-localization-to-the-plasma-membrane-of-nav-1-5-promoted-by-the-%C3%AE-2-subunit-is-defective-due-to-a-%C3%AE-2-mutation-associated-with-brugada-syndrome
#5
Gemma Dulsat, Sonia Palomeras, Eric Cortada, Helena Riuró, Ramon Brugada, Marcel Vergés
BACKGROUND INFORMATION: Cardiac channelopathies arise by mutations in genes encoding ion channel subunits. One example is Brugada Syndrome (BrS), which causes arrhythmias and sudden death. BrS is often associated with mutations in SCN5A, encoding Nav 1.5, the α subunit of the major cardiac voltage-gated sodium channel. This channel forms a protein complex including one or two associated β subunits as well as other proteins. RESULTS: We analyzed regulation of Nav 1...
June 9, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28596573/fibroblast-growth-factor-23-weakens-chemotaxis-of-human-blood-neutrophils-in-microfluidic-devices
#6
Ke Yang, Hagit Peretz-Soroka, Jiandong Wu, Ling Zhu, Xueling Cui, Michael Zhang, Claudio Rigatto, Yong Liu, Francis Lin
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592941/the-plant-cellular-systems-for-plant-virus-movement
#7
REVIEW
Jin-Sung Hong, Ho-Jong Ju
Plasmodesmata (PDs) are specialized intercellular channels that facilitate the exchange of various molecules, including sugars, ribonucleoprotein complexes, transcription factors, and mRNA. Their diameters, estimated to be 2.5 nm in the neck region, are too small to transfer viruses or viral genomes. Tobacco mosaic virus and Potexviruses are the most extensively studied viruses. In viruses, the movement protein (MP) is responsible for the PD gating that allows the intercellular movement of viral genomes. Various host factors interact with MP to regulate complicated mechanisms related to PD gating...
June 2017: Plant Pathology Journal
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#8
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
June 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28576298/intracellular-trafficking-pathways-of-cx43-gap-junction-channels
#9
Irina Epifantseva, Robin Shaw
Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling...
May 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28571716/post-translational-dysfunctions-in-channelopathies-of-the-nervous-system
#10
REVIEW
Benedetta Terragni, Paolo Scalmani, Silvana Franceschetti, Sandrine Cestèle, Massimo Mantegazza
Channelopathies comprise various diseases caused by defects of ion channels. Modifications of their biophysical properties are common and have been widely studied. However, ion channels are heterogeneous multi-molecular complexes that are extensively modulated and undergo a maturation process comprising numerous steps of structural modifications and intracellular trafficking. Perturbations of these processes can give rise to aberrant channels that cause pathologies. Here we review channelopathies of the nervous system associated with dysfunctions at the post-translational level (folding, trafficking, degradation, subcellular localization, interactions with associated proteins and structural post-translational modifications)...
May 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28559331/the-potra-domains-of-toc75-exhibit-chaperone-like-function-to-facilitate-import-into-chloroplasts
#11
Patrick K O'Neil, Lynn G L Richardson, Yamuna D Paila, Grzegorz Piszczek, Srinivas Chakravarthy, Nicholas Noinaj, Danny Schnell
Protein trafficking across membranes is an essential function in cells; however, the exact mechanism for how this occurs is not well understood. In the endosymbionts, mitochondria and chloroplasts, the vast majority of proteins are synthesized in the cytoplasm as preproteins and then imported into the organelles via specialized machineries. In chloroplasts, protein import is accomplished by the TOC (translocon on the outer chloroplast membrane) and TIC (translocon on the inner chloroplast membrane) machineries in the outer and inner envelope membranes, respectively...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28555925/functional-severity-of-clcnkb-mutations-correlates-with-phenotypes-in-patients-with-classic-bartter-s-syndrome
#12
Chih-Jen Cheng, Yi-Fen Lo, Jen-Chi Chen, Chou-Long Huang, Shih-Hua Lin
Mutations in CLCNKB gene encoding human voltage-gated chloride ClC-Kb (hClC-Kb) channel cause classic Bartter's syndrome (BS). In contrast to antenatal BS, classic BS manifests highly variable phenotypes. The functional severity of mutant channel has been proposed to explain this phenomenon. Due to difficulties in the expression of hClC-Kb in heterologous expression systems, the functional consequences of mutant channels haven't been thoroughly examined, and the genotype-phenotype association hasn't been established...
May 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28550110/trpm8-inhibits-endothelial-cell-migration-via-a-non-channel-function-by-trapping-the-small-gtpase-rap1
#13
Tullio Genova, Guillaume P Grolez, Chiara Camillo, Michela Bernardini, Alexandre Bokhobza, Elodie Richard, Marco Scianna, Loic Lemonnier, Donatella Valdembri, Luca Munaron, Mark R Philips, Virginie Mattot, Guido Serini, Natalia Prevarskaya, Dimitra Gkika, Alessandra Fiorio Pla
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function...
May 26, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28546447/signal-motifs-dependent-er-export-of-qc-snare-bet12-interacts-with-memb12-and-affects-pr1-trafficking-in-arabidopsis
#14
Kin Pan Chung, Yonglun Zeng, Yimin Li, Changyang Ji, Yiji Xia, Liwen Jiang
SNAREs are well-known for their role in controlling membrane fusion, the final but crucial step for vesicular transport in eukaryotes. SNARE proteins contribute to various biological processes including pathogen defense, channel activity regulation as well as plant growth and development. Precise targeting of SNARE proteins to destined compartments is a prerequisite for their proper functioning. However, the underlying mechanism(s) for SNAREs targeting in plants remains obscure. Here we investigate the targeting mechanism of the Qc-SNARE BET12, which is involved in protein trafficking in the early secretory pathway...
May 25, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28544109/express-with-caution-epitope-tags-and-cdna-variants-effects-on-herg-channel-trafficking-half-life-and-function
#15
Marika L Osterbur Badhey, Alexander C Bertalovitz, Thomas V McDonald
INTRODUCTION: Genetic mutations in KCNQ2 which encodes hERG, the alpha subunit of the potassium channel responsible for the IKr current, cause Long QT Syndrome, an inherited cardiac arrhythmia disorder. Electrophysiology techniques are used to correlate genotype with molecular phenotype to determine which mutations identified in patients diagnosed Long QT Syndrome are disease causing, and which are benign. These investigations are usually done using heterologous expression in cell lines, and often, epitope fusion tags are used to enable isolation and identification of the protein of interest...
May 24, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28535735/clenbuterol-attenuates-herg-channel-by-promoting-the-mature-channel-degradation
#16
Ling Luo, Peijing Hu, Changqing Miao, Aiqun Ma, Tingzhong Wang
Clenbuterol, a β2-selective adrenergic receptor agonist, is illicitly used in weight loss and performance enhancement and animal production. Increasing evidence demonstrates that clenbuterol induces various kinds of arrhythmias and QTc interval prolongation. However, little is known about the underlying mechanism. Most drugs are associated with QTc prolongation through interfering with human ether-a-go-go-related gene (hERG) K(+) channels. The present study aims to investigate the effects and underlying mechanisms of clenbuterol on the hERG channel...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28529828/two-pore-channels-and-parkinson-s-disease-where-s-the-link
#17
Pilar Rivero-Ríos, Belén Fernández, Jesús Madero-Pérez, María Romo Lozano, Sabine Hilfiker
Two-pore channels are endolysosomal Ca(2+) release channels involved in proper trafficking to and from those organelles. They are the likely targets for the Ca(2+)-mobilizing messenger NAADP, and are further regulated by a variety of mechanisms including phosphoinositide levels and Rab proteins. As discussed here, recent studies highlight a role for these channels in the pathomechanism(s) underlying Parkinson's disease, with important implications for possible alternative treatment strategies.
June 1, 2016: Messenger
https://www.readbyqxmd.com/read/28529827/deviant-lysosomal-ca-2-signalling-in-neurodegeneration-an-introduction
#18
Sandip Patel
Lysosomes are key acidic Ca(2+) stores. The principle Ca(2+)-permeable channels of the lysosome are TRP mucolipins (TRPMLs) and NAADP-regulated two-pore channels (TPCs). Recent studies, reviewed in this collection, have linked numerous neurodegenerative diseases to both gain and loss of function of TRPMLs/TPCs, as well as to defects in acidic Ca(2+) store content. These diseases span rare lysosomal storage disorders such as Mucolipidosis Type IV and Niemann-Pick disease, type C, through to more common ones such as Alzheimer and Parkinson disease...
June 1, 2016: Messenger
https://www.readbyqxmd.com/read/28526583/the-connexin-43-c-terminus-a-tail-of-many-tales
#19
REVIEW
Edward Leithe, Marc Mesnil, Trond Aasen
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28521126/structural-and-functional-architecture-of-ampa-type-glutamate-receptors-and-their-auxiliary-proteins
#20
REVIEW
Ingo H Greger, Jake F Watson, Stuart G Cull-Candy
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition...
May 17, 2017: Neuron
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