keyword
MENU ▼
Read by QxMD icon Read
search

Channel trafficking

keyword
https://www.readbyqxmd.com/read/28433559/the-kcnh2-ivs9-28a-g-mutation-causes-aberrant-isoform-expression-and-herg-trafficking-defect-in-cardiomyocytes-derived-from-patients-affected-by-long-qt-syndrome-type-2
#1
Manuela Mura, Ashish Mehta, Chrishan J Ramachandra, Rita Zappatore, Federica Pisano, Maria Chiara Ciuffreda, Vincenzo Barbaccia, Lia Crotti, Peter J Schwartz, Winston Shim, Massimiliano Gnecchi
BACKGROUND: Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2 gene that encodes for the α-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (IKr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown. METHODS AND RESULTS: We generated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G mutation carriers...
April 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28425222/class-iii-antiarrhythmic-drugs-amiodarone-and-dronedarone-impair-kir-2-1-backward-trafficking
#2
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
April 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28424266/disease-associated-extracellular-loop-mutations-in-the-adhesion-g-protein-coupled-receptor-g1-adgrg1-gpr56-differentially-regulate-downstream-signaling
#3
Ayush Kishore, Randy A Hall
Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria (BFPP). Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function, either through disruption of receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different BFPP-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (deltaNT) G1...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28423494/control-of-long-distance-cell-to-cell-communication-and-autophagosome-transfer-in-squamous-cell-carcinoma-via-tunneling-nanotubes
#4
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Eduardo Enciso, Inmaculada García-Moreno, Jose Luis Chiara, Carlos Suarez, María-Dolores Chiara
Tunneling nanotubes (TnTs) are thin channels that temporally connect nearby cells allowing the cell-to-cell trafficking of biomolecules and organelles. The presence or absence of TnTs in human neoplasms and the mechanisms of TnT assembly remains largely unexplored. In this study, we have identified TnTs in tumor cells derived from squamous cell carcinomas (SCC) cultured under bi-dimensional and tri-dimensional conditions and also in human SCC tissues. Our study demonstrates that TnTs are not specific of epithelial or mesenchymal phenotypes and allow the trafficking of endosomal/lysosomal vesicles, mitochondria, and autophagosomes between both types of cells...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421997/laser-microdissection-coupled-with-rna-seq-reveal-cell-type-and-disease-specific-markers-in-the-salivary-gland-of-sj%C3%A3-gren-s-syndrome-patients
#5
Mayank Tandon, Paola Perez, Peter D Burbelo, Catherine Calkins, Ilias Alevizos
OBJECTIVES: Little is known about the molecular details regarding the contribution of different cell types of the salivary gland to the altered gene expression profile seen in Sjögren's syndrome (SS). METHODS: Using laser microdissection, tissue samples enriched in acini, ducts and inflammatory foci in subjects with and without SS were isolated for RNA-seq analysis. Gene expression profiles were analysed and selected enriched genes were further examined using real time PCR and by immunofluorescence...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28420608/the-molecular-mechanisms-of-plant-plasma-membrane-intrinsic-proteins-trafficking-and-stress-response
#6
Wang Xing, Zhang Jilong, Feng Xiuxiu, Li Hongjie, Zhang Genfa
Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses...
April 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28397788/over-expression-of-microrna-1-causes-arrhythmia-by-disturbing-intracellular-trafficking-system
#7
Xiaomin Su, Haihai Liang, He Wang, Guizhi Chen, Hua Jiang, Qiuxia Wu, Tianyi Liu, Qiushuang Liu, Tong Yu, Yunyan Gu, Baofeng Yang, Hongli Shan
Dysregulation of intracellular trafficking system plays a fundamental role in the progression of cardiovascular disease. Up-regulation of miR-1 contributes to arrhythmia, we sought to elucidate whether intracellular trafficking contributes to miR-1-driven arrhythmia. By performing microarray analyses of the transcriptome in the cardiomyocytes-specific over-expression of microRNA-1 (miR-1 Tg) mice and the WT mice, we found that these differentially expressed genes in miR-1 Tg mice were significantly enrichment with the trafficking-related biological processes, such as regulation of calcium ion transport...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388411/architectures-of-lipid-transport-systems-for-the-bacterial-outer-membrane
#8
Damian C Ekiert, Gira Bhabha, Georgia L Isom, Garrett Greenan, Sergey Ovchinnikov, Ian R Henderson, Jeffery S Cox, Ronald D Vale
How phospholipids are trafficked between the bacterial inner and outer membranes through the hydrophilic space of the periplasm is not known. We report that members of the mammalian cell entry (MCE) protein family form hexameric assemblies with a central channel capable of mediating lipid transport. The E. coli MCE protein, MlaD, forms a ring associated with an ABC transporter complex in the inner membrane. A soluble lipid-binding protein, MlaC, ferries lipids between MlaD and an outer membrane protein complex...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28381826/recombinant-tandem-of-pore-domains-in-a-weakly-inward-rectifying-k-channel-2-twik2-forms-active-lysosomal-channels
#9
Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G Meuth, Florian Lesage
Recombinant TWIK2 channels produce weak basal background K(+) currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373283/distinct-domains-of-the-%C3%AE-1-subunit-cytosolic-n-terminus-control-surface-expression-and-functional-properties-of-large-conductance-calcium-activated-potassium-bk-channels
#10
Lie Chen, Danlei Bi, Zen Huat Lu, Heather McClafferty, Michael J Shipston
The properties and function of large conductance calcium- and voltage- activated potassium (BK) channels are modified by the tissue specific expression of regulatory β 1-subunits. Although the short cytosolic N-terminal domain of the β 1-subunit is important for controlling both BK channel trafficking and function, whether the same, or different, regions of the N-terminus control these distinct processes remain unknown. Here we demonstrate that the first six N-terminal residues, including K3, K4 and L5, are critical for controlling functional regulation, but not trafficking, of BK channels...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28372301/endoplasmic-reticulum-retention-of-kcnq2-potassium-channel-mutants-following-temperature-elevation
#11
Fang Yu, Jian Xu, Zheman Xiao, Biwen Peng, Xiaohua He
BACKGROUND: KCNQ2 plays a key role in the regulation of neuronal excitability. The R214W and Y284C mutants of KCNQ2 channels, which are associated with BFNC, can decrease channel function to cause neuronal hyperexcitability and promote seizures. Previous studies revealed that elevated temperature caused up-regulation of KCNQ2 expression. OBJECTIVE: The present study sought to investigate the impact of temperature elevation on neuronal KCNQ2 ion channel mutants. METHODS: Protein expression of wt KCNQ2 and the R214W, Y284C and truncated selective filter mutants at different temperatures was detected by live-cell confocal fluorescence microscopy and by Western blotting...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28370132/infant-sudden-death-mutations-responsible-for-impaired-nav1-5-channel-trafficking-and-function
#12
Ivan Gando, Jace Morganstein, Kundan Jana, Thomas V McDonald, Yingying Tang, William A Coetzee
BACKGROUND: Two genetic variants in SCN5A, encoding the Nav1.5 Na(+) channel α-subunit, were found in a five month-old girl who died suddenly in her sleep. The first variant is a missense mutation, resulting in an amino acid change (Q1832E), which has been described (but not characterized) in a patient with Brugada syndrome. The second is a nonsense mutation that produces a premature stop codon and a C-terminal truncation (R1944Δ). METHODS AND RESULTS: To investigate their functional relevance with patch clamp experiments in transfected HEK293 cells...
March 31, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28366665/the-phe932ile-mutation-in-kcnt1-channels-associated-with-severe-epilepsy-delayed-myelination-and-leukoencephalopathy-produces-a-loss-of-function-channel-phenotype
#13
Katherine M Evely, Kerri D Pryce, Arin Bhattacharjee
Sodium-activated potassium (KNa) channels contribute to firing frequency adaptation and slow after hyperpolarization. The KCNT1 gene (also known as SLACK) encodes a KNa subunit that is expressed throughout the central and peripheral nervous systems. Missense mutations of the SLACK C-terminus have been reported in several patients with rare forms of early onset epilepsy and in some cases severely delayed myelination. To date, such mutations identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), epilepsy of infancy with migrating focal seizures (EIMFS) and Ohtahara syndrome (OS) have been reported to be gain-of-function mutations (Villa and Combi, 2016)...
March 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28363979/densin-180-controls-the-trafficking-and-signaling-of-l-type-voltage-gated-cav1-2-ca-2-channels-at-excitatory-synapses
#14
Shiyi Wang, Ruslan I Stanika, Xiaohan Wang, Jussara Hagen, Mary B Kennedy, Gerald J Obermair, Roger J Colbran, Amy Lee
Voltage-gated Cav1.2 and Cav1.3 (L-type) Ca(2+) channels regulate neuronal excitability, synaptic plasticity, and learning and memory. Densin-180 (densin) is an excitatory synaptic protein that promotes Ca(2+)-dependent facilitation of voltage-gated Cav1.3 Ca(2+) channels in transfected cells. Mice lacking densin (densin KO) exhibit defects in synaptic plasticity, spatial memory, and increased anxiety-related behaviors --phenotypes that more closely match those in mice lacking Cav1.2 than Cav1.3. Thus, we investigated the functional impact of densin on Cav1...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28360104/the-lysosomal-ca2-release-channel-trpml1-regulates-lysosome-size-by-activating-calmodulin
#15
Qi Cao, Yiming Yang, Xi Zoë Zhong, Xian-Ping Dong
Intracellular lysosomal membrane trafficking, including fusion and fission, is crucial for cellular homeostasis and normal cell function. Both fusion and fission of lysosomal membrane are accompanied by lysosomal Ca2+ release. We recently have demonstrated that the lysosomal Ca2+ release channel P2X4 regulates lysosome fusion through a calmodulin (CaM)-dependent mechanism. However, the molecular mechanism underlying lysosome fission remains uncertain. In this study, we report that enlarged lysosomes/vacuoles induced by either vacuolin-1 or P2X4 activation are suppressed by upregulating the lysosomal Ca2+ release channel transient receptor potential mucolipin 1 (TRPML1), but not the lysosomal Na+ release channel two pore channel 2 (TPC2)...
March 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#16
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/28346351/in-vitro-and-in-vivo-studies-on-the-structural-organization-of-chs3-from-saccharomyces-cerevisiae
#17
Simon Gohlke, Subbaratnam Muthukrishnan, Hans Merzendorfer
Chitin biosynthesis in yeast is accomplished by three chitin synthases (Chs) termed Chs1, Chs2 and Chs3, of which the latter accounts for most of the chitin deposited within the cell wall. While the overall structures of Chs1 and Chs2 are similar to those of other chitin synthases from fungi and arthropods, Chs3 lacks some of the C-terminal transmembrane helices raising questions regarding its structure and topology. To fill this gap of knowledge, we performed bioinformatic analyses and protease protection assays that revealed significant information about the catalytic domain, the chitin-translocating channel and the interfacial helices in between...
March 25, 2017: International Journal of Molecular Sciences
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
#18
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/28342809/identity-and-function-of-a-cardiac-mitochondrial-small-conductance-ca-2-activated-k-channel-splice-variant
#19
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/28331084/structural-insights-into-emerging-pediatric-pathogens-human-bocaparvoviruses
#20
Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna
Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 gastrointestinal infections in young children. Recent reports of life threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2...
March 22, 2017: Journal of Virology
keyword
keyword
6059
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"