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https://www.readbyqxmd.com/read/29352299/bunyavirus-requirement-for-endosomal-k-reveals-new-roles-of-cellular-ion-channels-during-infection
#1
Samantha Hover, Becky Foster, Juan Fontana, Alain Kohl, Steve A N Goldstein, John N Barr, Jamel Mankouri
In order to multiply and cause disease a virus must transport its genome from outside the cell into the cytosol, most commonly achieved through the endocytic network. Endosomes transport virus particles to specific cellular destinations and viruses exploit the changing environment of maturing endocytic vesicles as triggers to mediate genome release. Previously we demonstrated that several bunyaviruses, which comprise the largest family of negative sense RNA viruses, require the activity of cellular potassium (K+) channels to cause productive infection...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29349559/a-mutant-hcn4-channel-in-a-family-with-bradycardia-left-bundle-branch-block-and-left-ventricular-noncompaction
#2
Ryosuke Yokoyama, Koshi Kinoshita, Yukiko Hata, Masayoshi Abe, Kenta Matsuoka, Keiichi Hirono, Masanobu Kano, Makoto Nakazawa, Fukiko Ichida, Naoki Nishida, Toshihide Tabata
We found that a female infant presenting with left bundle branch block and left ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E), SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible pathogenicity of HCN4(G811E), which results in a G811E substitution in hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole-cell HCN4 channel conductance, whereas it did not affect the gating kinetics, unitary conductance, or cAMP-dependent modulation of voltage-dependence...
January 18, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice
#3
Alexandros H Kanellopoulos, Jennifer Koenig, Honglei Huang, Martina Pyrski, Queensta Millet, Stéphane Lolignier, Toru Morohashi, Samuel J Gossage, Maude Jay, John E Linley, Georgios Baskozos, Benedikt M Kessler, James J Cox, Annette C Dolphin, Frank Zufall, John N Wood, Jing Zhao
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1...
January 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#4
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29311259/the-endosomal-trafficking-factors-corvet-and-escrt-suppress-plasma-membrane-residence-of-the-renal-outer-medullary-potassium-channel-romk
#5
Timothy D Mackie, Bo-Young Kim, Arohan R Subramanya, Daniel J Bain, Allyson F O'Donnell, Paul A Welling, Jeffrey L Brodsky
Protein trafficking can act as the primary regulatory mechanism for ion channels with high open probabilities, such as the renal outer medullary (ROMK) channel. ROMK, also known as Kir1.1 (KCNJ1), is the major route for potassium secretion into the pro-urine and plays an indispensable role in regulating serum potassium and urinary concentrations. However, the cellular machinery that regulates ROMK trafficking has not been fully defined. To identify regulators of the cell-surface population of ROMK, we expressed a pH-insensitive version of the channel in the budding yeast Saccharomyces cerevisiae...
January 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29303993/endolysosomal-cation-channels-and-cancer-a-link-with-great-potential
#6
REVIEW
Christian Grimm, Karin Bartel, Angelika M Vollmar, Martin Biel
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism...
January 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29301848/physiologic-pathologic-and-therapeutic-paracrine-modulation-of-cardiac-excitation-contraction-coupling
#7
REVIEW
Joshua Mayourian, Delaine K Ceholski, David M Gonzalez, Timothy J Cashman, Susmita Sahoo, Roger J Hajjar, Kevin D Costa
Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular trafficking, and subsequent sarcomere shortening and myofibrillar contraction. Neurohumoral β-adrenergic signaling is a well-established mediator of ECC; other signaling mechanisms, such as paracrine signaling, have also demonstrated significant impact on ECC but are less well understood. For example, resident heart endothelial cells are well-known physiological paracrine modulators of cardiac myocyte ECC mainly via NO and endothelin-1...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29296759/a-specialized-pathway-for-erythroid-iron-delivery-through-lysosomal-trafficking-of-transferrin-receptor-2
#8
Shadi Khalil, Maja Holy, Stephen Grado, Robert Fleming, Ryo Kurita, Yukio Nakamura, Adam Goldfarb
Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released, reduced, and exported to the cytosol via DMT1. However, mice lacking TfR1 or DMT1 demonstrate residual erythropoiesis, suggesting additional pathways for iron use...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290926/trafficking-of-bk-channel-subunits-controls-arterial-contractility
#9
EDITORIAL
M Dennis Leo, Jonathan H Jaggar
No abstract text is available yet for this article.
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288344/fdc-tfh-interactions-within-cervical-lymph-nodes-of-siv-infected-rhesus-macaques
#10
Rajnish S Dave, Ravi K Sharma, Roshell R Muir, Elias Haddad, Sanjeev Gumber, Francois Villinger, Artinder P Nehra, Zafar K Khan, Brian Wigdahl, Aftab A Ansari, Siddappa N Byrareddy, Pooja Jain
Cerebrospinal fluid (CSF) drains via the lymphatic drainage pathway. This lymphatic pathway connects the central nervous system (CNS) to the cervical lymph node (CLN). As the CSF drains to CLN via the dural and nasal lymphatics, T cells and antigen presenting cells pass along the channels from the subarachnoid space through the cribriform plate. Human immunodeficiency virus (HIV) may also egress from the CNS along this pathway. As a result, HIV egressing from the CNS may accumulate within the CLN. Towards this objective, we analyzed CLNs isolated from rhesus macaques that were chronically-infected with simian immunodeficiency virus (SIV)...
December 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29280343/the-ropae-gene-encodes-a-porin-like-protein-involved-in-copper-transit-in-rhizobium-etli-cfn42
#11
Antonio González-Sánchez, Ciro A Cubillas, Fabiola Miranda, Araceli Dávalos, Alejandro García-de Los Santos
Copper (Cu) is an essential micronutrient for all aerobic forms of life. Its oxidation states (Cu+ /Cu2+ ) make this metal an important cofactor of enzymes catalyzing redox reactions in essential biological processes. In gram-negative bacteria, Cu uptake is an unexplored component of a finely regulated trafficking network, mediated by protein-protein interactions that deliver Cu to target proteins and efflux surplus metal to avoid toxicity. Rhizobium etliCFN42 is a facultative symbiotic diazotroph that must ensure its appropriate Cu supply for living either free in the soil or as an intracellular symbiont of leguminous plants...
December 27, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/29259251/bkip-1-an-auxiliary-subunit-critical-to-slo-1-function-inhibits-slo-2-potassium-channel-in-vivo
#12
Long-Gang Niu, Ping Liu, Yuan Shui, Roger Mailler, Zhao-Wen Wang, Bojun Chen
Auxiliary subunits are often needed to tailor K+ channel functional properties and expression levels. Many auxiliary subunits have been identified for mammalian Slo1, a high-conductance K+ channel gated by voltage and Ca2+. Experiments with heterologous expression systems show that some of the identified Slo1 auxiliary subunits can also regulate other Slo K+ channels. However, it is unclear whether a single auxiliary subunit may regulate more than one Slo channel in native tissues. BKIP-1, an auxiliary subunit of C...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229864/cytoplasmic-cl-couples-membrane-remodeling-to-epithelial-morphogenesis
#13
Mu He, Wenlei Ye, Won-Jing Wang, Eirish S Sison, Yuh Nung Jan, Lily Yeh Jan
Chloride is the major free anion in the extracellular space (>100 mM) and within the cytoplasm in eukaryotes (10 ∼ 20 mM). Cytoplasmic Cl- level is dynamically regulated by Cl- channels and transporters. It is well established that movement of Cl- across the cell membrane is coupled with cell excitability through changes in membrane potential and with water secretion. However, whether cytoplasmic Cl- plays additional roles in animal development and tissue homeostasis is unknown. Here we use genetics, cell biological and pharmacological tools to demonstrate that TMEM16A, an evolutionarily conserved calcium-activated chloride channel (CaCC), regulates cytoplasmic Cl- homeostasis and promotes plasma membrane remodeling required for mammalian epithelial morphogenesis...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29218789/precise-localizations-of-voltage-gated-sodium-and-potassium-channels-in-neurons
#14
REVIEW
Hiroaki Misonou
Neurons are extremely large and complex cells, and they regulate membrane potentials in multiple subcellular compartments using a variety of ion channels. Voltage-gated sodium (Nav) and potassium (Kv) channels are crucial in regulating neuronal membrane excitability owing to their diversity in subtypes, biophysical properties, and localizations. In particular, specific localizations of Nav and Kv channels in specific membrane compartments are essential to achieve a precise control of local membrane excitability...
December 8, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29208685/nonmuscle-myosin-2-proteins-encoded-by-myh9-myh10-and-myh14-are-uniquely-distributed-in-the-tubular-segments-of-murine-kidney
#15
Karla L Otterpohl, Ryan G Hart, Claire Evans, Kameswaran Surendran, Indra Chandrasekar
The diverse epithelial cell types of the kidneys are segregated into nephron segments and the collecting ducts in order to endow each tubular segment with unique functions. The rich diversity of the epithelial cell types is highlighted by the unique membrane channels and receptors expressed within each nephron segment. Our previous work identified a critical role for Myh9 and Myh10 in mammalian endocytosis. Here, we examined the expression patterns of Nonmuscle myosin 2 (NM2) heavy chains encoded by Myh9, Myh10, and Myh14 in mouse kidneys as these genes may confer unique nephron segment-specific membrane transport properties...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29199957/the-ampa-receptor-associated-protein-shisa7-regulates-hippocampal-synaptic-function-and-contextual-memory
#16
Leanne J M Schmitz, Remco V Klaassen, Marta Ruiperez-Alonso, Azra Elia Zamri, Jasper Stroeder, Priyanka Rao-Ruiz, Johannes C Lodder, Rolinka J van der Loo, Huib D Mansvelder, August B Smit, Sabine Spijker
Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression...
December 4, 2017: ELife
https://www.readbyqxmd.com/read/29198882/adjuvant-effect-of-short-chain-triacylglycerol-tributyrin-on-a-mouse-contact-hypersensitivity-model
#17
Kota Sekiguchi, Erina Ogawa, Kohta Kurohane, Hideyuki Konishi, Narumi Mochizuki, Kei Manabe, Yasuyuki Imai
Little attention has been paid to chemicals that can enhance hypersensitivity caused by other chemicals. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such an enhancing effect were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels, which are expressed on a part of sensory neurons, using a TRPA1-expressing cell line. In this study, we examined these activities of esters comprising glycerol and a short chain fatty acid, i...
November 30, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29184507/kir2-1-nav1-5-channel-complexes-are-differently-regulated-than-kir2-1-and-nav1-5-channels-alone
#18
Raquel G Utrilla, Paloma Nieto-Marín, Silvia Alfayate, David Tinaquero, Marcos Matamoros, Marta Pérez-Hernández, Sandra Sacristán, Lorena Ondo, Raquel de Andrés, F Javier Díez-Guerra, Juan Tamargo, Eva Delpón, Ricardo Caballero
Cardiac Kir2.1 and Nav1.5 channels generate the inward rectifier K+ (IK1) and the Na+ (INa) currents, respectively. There is a mutual interplay between the ventricular INa and IK1 densities, because Nav1.5 and Kir2.1 channels exhibit positive reciprocal modulation. Here we compared some of the biological properties of Nav1.5 and Kir2.1 channels when they are expressed together or separately to get further insights regarding their putative interaction. First we demonstrated by proximity ligation assays (PLAs) that in the membrane of ventricular myocytes Nav1...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29172645/a-homogeneous-cell-based-halide-sensitive-yellow-fluorescence-protein-assay-to-identify-modulators-of-the-cystic-fibrosis-transmembrane-conductance-regulator-ion-channel
#19
Emery Smith, Kenneth A Giuliano, Justin Shumate, Pierre Baillargeon, Brigid McEwan, Matthew D Cullen, John P Miller, Lawrence Drew, Louis Scampavia, Timothy P Spicer
Cystic fibrosis (CF), an inherited genetic disease, is caused by mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes an ion channel involved in hydration maintenance by anion homeostasis. Ninety percent of CF patients possess one or more copies of the F508del CFTR mutation. This mutation disrupts trafficking of the protein to the plasma membrane and diminishes function of mature CFTR. Identifying small molecule modulators of mutant CFTR activity or biosynthesis may yield new tools for discovering novel CF treatments...
November 27, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29166605/l-type-voltage-gated-ca2-channels-regulate-synaptic-activity-triggered-recycling-endosome-fusion-in-neuronal-dendrites
#20
Brian G Hiester, Ashley M Bourke, Brooke L Sinnen, Sarah G Cook, Emily S Gibson, Katharine R Smith, Matthew J Kennedy
The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs) with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs) regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface...
November 21, 2017: Cell Reports
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