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https://www.readbyqxmd.com/read/29166605/l-type-voltage-gated-ca-2-channels-regulate-synaptic-activity-triggered-recycling-endosome-fusion-in-neuronal-dendrites
#1
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 Ca(2+) from distinct sources. NMDA receptor Ca(2+) initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca(2+) 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
https://www.readbyqxmd.com/read/29163049/tagging-of-endogenous-bk-channels-with-a-fluorogen-activating-peptide-reveals-%C3%AE-4-mediated-control-of-channel-clustering-in-cerebellum
#2
Christopher P Pratt, Dika A Kuljis, Gregg E Homanics, Jianjun He, Dmytro Kolodieznyi, Srikanth Dudem, Mark A Hollywood, Alison L Barth, Marcel P Bruchez
BK channels are critical regulators of neuronal activity, controlling firing, neurotransmitter release, cerebellar function, and BK channel mutations have been linked to seizure disorders. Modulation of BK channel gating is well characterized, regulated by accessory subunit interactions, intracellular signaling pathways, and membrane potential. In contrast, the role of intracellular trafficking mechanisms in controlling BK channel function, especially in live cells, has been less studied. Fluorogen-activating peptides (FAPs) are well-suited for trafficking and physiological studies due to the binding of malachite green (MG)-based dyes with sub-nanomolar affinity to the FAP, resulting in bright, photostable, far-red fluorescence...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162902/shear-stress-regulates-trpv4-channel-clustering-and-translocation-from-adherens-junctions-to-the-basal-membrane
#3
Sara Baratchi, Markus Knoerzer, Khashayar Khoshmanesh, Arnan Mitchell, Peter McIntyre
Localized Ca(2+) influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29155857/impaired-aqp2-trafficking-in-fxyd1-knockout-mice-a-role-for-fxyd1-in-regulated-vesicular-transport
#4
Elena Arystarkhova, Richard Bouley, Yi Bessie Liu, Kathleen J Sweadner
The final adjustment of urine volume occurs in the inner medullary collecting duct (IMCD), chiefly mediated by the water channel aquaporin 2 (AQP2). With vasopressin stimulation, AQP2 accumulation in the apical plasma membrane of principal cells allows water reabsorption from the lumen. We report that FXYD1 (phospholemman), better known as a regulator of Na,K-ATPase, has a role in AQP2 trafficking. Daytime urine of Fxyd1 knockout mice was more dilute than WT despite similar serum vasopressin, but both genotypes could concentrate urine during water deprivation...
2017: PloS One
https://www.readbyqxmd.com/read/29146210/novel-intracellular-transport-refractory-mutations-in-kcnh2-identified-in-patients-with-symptomatic-long-qt-syndrome
#5
Daisuke Fukumoto, Wei-Guang Ding, Yuko Wada, Yusuke Fujii, Mari Ichikawa, Koichiro Takayama, Megumi Fukuyama, Koichi Kato, Hideki Itoh, Takeru Makiyama, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Minoru Horie, Seiko Ohno
BACKGROUND: Missense mutations in KCNH2, a gene encoding the Kv11.1 channel, cause long QT syndrome (LQTS) type 2 primarily by disrupting the intracellular transport of Kv11.1 to the plasma membrane. The present study aimed to clarify the functional changes by two novel KCNH2 missense mutations. METHODS: We performed genetic screening of three unrelated symptomatic LQTS probands with family histories of cardiac symptoms. Chinese hamster ovary cells were transfected with wild-type (WT) and/or mutant KCNH2 plasmid and examined by patch-clamp technique...
November 13, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#6
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29138928/mechanisms-of-drug-binding-to-voltage-gated-sodium-channels
#7
M E O'Leary, M Chahine
Voltage-gated sodium (Na(+)) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. Genetic disorders that disrupt the function of these channels produce an array of Na(+) channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. Because of their importance to the conduction of electrical signals, Na(+) channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs...
November 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#8
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29129580/the-%C3%AE-and-%C3%AE-2%C3%AE-auxiliary-subunits-of-cav1-channels-are-required-for-th2-lymphocyte-function-and-acute-allergic-airway-inflammation
#9
Nicolas Rosa, Emily Triffaux, Virginie Robert, Marion Mars, Martin Klein, Gregory Bouchaud, Astrid Canivet, Antoine Magnan, Jean-Charles Guéry, Lucette Pelletier, Magali Savignac
BACKGROUND: T-lymphocytes express not only the cell membrane calcium ORAI1 but also voltage-dependent Cav1 channels. In excitable cells, these channels are composed of the ion forming pore α1 and auxiliary subunits (β and α2δ) needed for proper trafficking and activation of the channel. We previously disclosed the role of Cav1.2 α1 in mouse and human Th2- but not Th1-cell functions and showed that knocking-down Cav1 α1 prevents experimental asthma OBJECTIVE: We investigated the role of β and α2δ auxiliary subunits on Cav1 α1 function in Th2 lymphocytes and on the development of acute allergic airway inflammation...
November 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29110470/emerging-functional-differences-between-the-synaptotagmin-and-ferlin-calcium-sensor-families
#10
Colin P Johnson
The ferlin family of proteins have emerged as multi-C2 domain regulators of calcium triggered membrane fusion and fission events. While initially determined to share many of the features of the synaptotagmins family of calcium sensors, more recent studies have determined that ferlins directly interact with non-neuronal voltage gated calcium channels and nucleate the assembly of membrane trafficking protein complexes, functions that distinguish them from the more well studied synaptotagmins family. Here we highlight some of the recent findings that have advanced our understanding of ferlins and their functional differences with the synaptotagmins family...
November 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/29109154/hierarchical-protein-targeting-and-secretion-is-controlled-by-an-affinity-switch-in-the-type-iii-secretion-system-of-enteropathogenic-escherichia-coli
#11
Athina G Portaliou, Konstantinos C Tsolis, Maria S Loos, Vassileia Balabanidou, Josep Rayo, Alexandra Tsirigotaki, Valerie F Crepin, Gad Frankel, Charalampos G Kalodimos, Spyridoula Karamanou, Anastassios Economou
Type III secretion (T3S), a protein export pathway common to Gram-negative pathogens, comprises a trans-envelope syringe, the injectisome, with a cytoplasm-facing translocase channel. Exported substrates are chaperone-delivered to the translocase, EscV in enteropathogenic Escherichia coli, and cross it in strict hierarchical manner, for example, first "translocators", then "effectors". We dissected T3S substrate targeting and hierarchical switching by reconstituting them in vitro using inverted inner membrane vesicles...
November 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29107716/pacsin-2-is-required-for-the-maintenance-of-a-normal-cardiac-function-in-the-developing-mouse-heart
#12
Judith Semmler, Jan Kormann, Sureshkumar Perumal Srinivasan, Annette Köster, Daniel Sälzer, Michael Reppel, Jürgen Hescheler, Markus Plomann, Filomain Nguemo
The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT)...
October 28, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29103957/basolateral-cholesterol-depletion-alters-aquaporin-2-post-translational-modifications-and-disrupts-apical-plasma-membrane-targeting
#13
Hanne B Moeller, Cecilia Hvitfeldt Fuglsang, Cecilie Nøhr Pedersen, Robert A Fenton
Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation...
November 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29102663/signaling-pathways-relevant-to-nerve-growth-factor-induced-upregulation-of-transient-receptor-potential-m8-expression
#14
Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Jin Nakahara, Toshihiko Shimizu, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that primarily detects the innocuous cold. In pathological conditions, TRPM8 plays a role in the development of cold hyperalgesia/allodynia. Nerve growth factor (NGF) is an important mediator involved in various pain disorders. In the present study, the NGF-TrkA pathway increased TRPM8 expression by stabilizing TRPM8 mRNA through the actions of phosphatidylinositol 3-kinase and p38 MAP kinase. Moreover, c-Jun N-terminal kinase and Src tyrosine kinase were identified as a positive and negative regulator of TRPM8 expression, respectively, via post-transcriptional mechanisms independent of mRNA stabilization...
November 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/29100505/optical-inhibition-of-larval-zebrafish-behaviour-with-anion-channelrhodopsins
#15
Gadisti Aisha Mohamed, Ruey-Kuang Cheng, Joses Ho, Seetha Krishnan, Farhan Mohammad, Adam Claridge-Chang, Suresh Jesuthasan
BACKGROUND: Optical silencing of activity provides a way to test the necessity of neurons in behaviour. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown to potently inhibit activity in cultured mammalian neurons and in Drosophila. Here, we test the usefulness of these channels in larval zebrafish, using spontaneous coiling behaviour as the assay. RESULTS: When the GtACRs were expressed in spinal neurons of embryonic zebrafish and actuated with blue or green light, spontaneous movement was inhibited...
November 3, 2017: BMC Biology
https://www.readbyqxmd.com/read/29097308/analysis-of-natural-product-regulation-of-opioid-receptors-in-the-treatment-of-human-disease
#16
REVIEW
S Badal, S Turfus, R Rajnarayanan, C Wilson-Clarke, S L Sandiford
Opioid receptors (ORs), μOR, δOR, κOR and ORL1 mediate numerous signaling cascades, most importantly, through the modulation of ion channels. Research demonstrates the role of OR mediated signal transduction in treating pain, cancer, neurodegenerative disorders and cardiac insults. Yet, the primary application of drugs that modulate ORs is analgesia. Current opioids like morphine that are mainly μOR orthosteric agonists attract many undesirable side-effects (constipation, urinary retention, respiratory depression and hypotension) and the existing modus operandi against these is the inclusion of a μOR antagonist (for example...
October 30, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29095109/pkc-and-calcium-channel-trafficking
#17
Franz Hofmann
No abstract text is available yet for this article.
November 2, 2017: Channels
https://www.readbyqxmd.com/read/29089904/ion-channel-trafficking-control-of-ion-channel-density-as-a-target-for-arrhythmias
#18
REVIEW
Elise Balse, Hannah E Boycott
The shape of the cardiac action potential (AP) is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP) and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29077056/aquaporin-protein-protein-interactions
#19
REVIEW
Jennifer Virginia Roche, Susanna Törnroth-Horsefield
Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein-protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein-protein interactions; dividing the interactions into three types: (1) interactions between aquaporin tetramers; (2) interactions between aquaporin monomers within a tetramer (hetero-tetramerization); and (3) transient interactions with regulatory proteins...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29070491/rhoa-increases-asic1a-plasma-membrane-localization-and-calcium-influx-in-pulmonary-arterial-smooth-muscle-cells-following-chronic-hypoxia
#20
Lindsay M Herbert, Thomas C Resta, Nikki L Jernigan
Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca(2+) levels and enhanced RhoA/Rho kinase-dependent Ca(2+) sensitization are key determinants of PASMC contraction, migration, and proliferation accompanying the development of hypoxic pulmonary hypertension. We have previously shown acid sensing ion channel 1a (ASIC1a)-mediated Ca(2+) entry in PASMC is an important constituent of the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension...
October 25, 2017: American Journal of Physiology. Cell Physiology
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