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https://www.readbyqxmd.com/read/28731156/protein-interacting-with-c%C3%A2-kinase-1-modulates-exocytosis-and-katp-conductance-in-pancreatic-%C3%AE-cells
#1
Yunhong Li, Fan Li, Bin Bai, Zhenyong Wu, Xiaolin Hou, Ying Shen, Yin Wang
It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28724750/disruption-of-a-structurally-important-extracellular-element-in-the-glycine-receptor-leads-to-decreased-synaptic-integration-and-signaling-resulting-in-severe-startle-disease
#2
Natascha Schaefer, Alexandra Berger, Johannes van Brederode, Fang Zheng, Yan Zhang, Sophie Leacock, Laura Littau, Sibylle Jablonka, Sony Malhotra, Maya Topf, Friederike Winter, Daria Davydova, Joseph W Lynch, Christopher J Paige, Christian Alzheimer, Robert J Harvey, Carmen Villmann
Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorder. We found that lack of synaptic integration of GlyRs, together with disrupted receptor function is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation Q177K located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in cys-loop receptors...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28722651/ephrin-a-epha-specific-co-adaptation-as-a-novel-mechanism-in-topographic-axon-guidance
#3
Felix Fiederling, Markus Weschenfelder, Martin Fritz, Anne von Philipsborn, Martin Bastmeyer, Franco Weth
Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28719054/evolutionary-cell-biology-of-proteins-from-protists-to-humans-and-plants
#4
REVIEW
Helmut Plattner
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas, for bikonts, ciliates are preferred models...
July 18, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28716860/novel-mechanisms-of-piezo1-dysfunction-in-hereditary-xerocytosis
#5
Edyta Glogowska, Eve R Schneider, Yelena Maksimova, Vincent P Schulz, Kimberly Lezon-Geyda, John Wu, Kottayam Radhakrishnan, Siobán B Keel, Donald Mahoney, Alison M Freidmann, Rachel A Altura, Elena O Gracheva, Sviatoslav N Bagriantsev, Theodosia A Kalfa, Patrick G Gallagher
Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We utilized next generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected HX and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore region domain. Several mutations were novel and demonstrated ethnic specificity. We characterized these mutations using genomic, bioinformatic, cell biology, and physiology-based functional assays...
July 17, 2017: Blood
https://www.readbyqxmd.com/read/28710278/phosphorylation-of-human-aquaporin-2-aqp2-allosterically-controls-its-interaction-with-the-lysosomal-trafficking-protein-lip5
#6
Jennifer Virginia Roche, Sabeen Survery, Stefan Kreida, Veronika Nesverova, Henry Ampah-Korsah, Maria Gourdon, Peter M T Deen, Susanna Toernroth-Horsefield
The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process which controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment. Vasopressin regulates phosphorylation at four sites within the AQP2 C-terminus (S256, S261, S264, T269), of which S256 is crucial and sufficient for AQP2 translocation from storage vesicles to the apical membrane...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28702049/endurance-exercise-ability-in-the-horse-a-trait-with-complex-polygenic-determinism
#7
Anne Ricard, Céline Robert, Christine Blouin, Fanny Baste, Gwendoline Torquet, Caroline Morgenthaler, Julie Rivière, Nuria Mach, Xavier Mata, Laurent Schibler, Eric Barrey
Endurance horses are able to run at more than 20 km/h for 160 km (in bouts of 30-40 km). This level of performance is based on intense aerobic metabolism, effective body heat dissipation and the ability to endure painful exercise. The known heritabilities of endurance performance and exercise-related physiological traits in Arabian horses suggest that adaptation to extreme endurance exercise is influenced by genetic factors. The objective of the present genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) related to endurance racing performance in 597 Arabian horses...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28701358/mechanism-of-action-of-the-anti-inflammatory-connexin43-mimetic-peptide-jm2
#8
J Matthew Rhett, Bennett W Calder, Stephen A Fann, Heather Bainbridge, Robert G Gourdie, Michael J Yost
Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43)-mimetic peptide JM2 reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell-surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28700952/nicotine-facilitates-nicotinic-acetylcholine-receptor-targeting-to-mitochondria-but-makes-them-less-susceptible-to-selective-ligands
#9
Kateryna Uspenska, Olena Lykhmus, Galyna Gergalova, Volodymyr Chernyshov, Hugo R Arias, Sergiy Komisarenko, Maryna Skok
Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The idea of the present work was to determine whether nicotine affects the content, glycosylation, and function of mitochondrial nAChRs...
July 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28697281/transport-of-the-alpha-subunit-of-the-l-type-calcium-channel-through-the-sarcoplasmic-reticulum-occurs-prior-to-localization-to-triads-and-requires-the-beta-subunit-but-not-stac3-in-skeletal-muscles
#10
Jeremy W Linsley, I-Uen Hsu, Wenjai Wang, John Y Kuwada
Contraction of skeletal muscle is initiated by excitation-contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca(2+) release. EC coupling requires dihydropyridine receptors (DHPR) located at triads, which are junctions between the transverse (T) tubule and SR membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies. The precise localization of DHPRs to triads is critical for EC coupling, yet trafficking of the DHPR to triads is not well understood...
July 11, 2017: Traffic
https://www.readbyqxmd.com/read/28696251/endothelin-1-stimulates-vasoconstriction-through-rab11a-serine-177-phosphorylation
#11
Xue Zhai, Marie D Leo, Jonathan H Jaggar
Rationale: Large-conductance calcium (Ca(2+))-activated potassium channels (BK) are composed of pore-forming BKα and auxiliary β1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKα is primarily plasma membrane-localized, whereas the cellular location of β1 can be rapidly altered by Rab11A-positive recycling endosomes. Whether vasoconstrictors regulate the multi-subunit composition of surface BK channels to stimulate contraction is unclear...
July 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28694772/connexin-dependent-neuroglial-networking-as-a-new-therapeutic-target
#12
REVIEW
Mathieu Charvériat, Christian C Naus, Luc Leybaert, Juan C Sáez, Christian Giaume
Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28689039/connexin43-but-not-connexin30-contributes-to-adult-neurogenesis-in-the-dentate-gyrus
#13
REVIEW
Jiong Zhang, Stephanie Griemsmann, Zhou Wu, Radoslaw Dobrowolski, Klaus Willecke, Martin Theis, Christian Steinhäuser, Peter Bedner
The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis...
July 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28688851/characterization-of-the-dominant-inheritance-mechanism-of-episodic-ataxia-type-2
#14
Kevin Dorgans, Julie Salvi, Federica Bertaso, Ludivine Bernard, Philippe Lory, Frederic Doussau, Alexandre Mezghrani
Episodic Ataxia type 2 (EA2) is an autosomal dominant neuronal disorder linked to mutations in the Cav2.1 subunit of P/Q-type calcium channels. In vitro studies have established that EA2 mutations induce loss of channel activity and that EA2 mutants can exert a dominant negative effect, suppressing normal Cav2.1 activity through protein misfolding and trafficking defects. To date, the role of this mechanism in the disease pathogenesis is unknown because no animal model exists. To address this issue, we have generated a mouse bearing the R1497X nonsense mutation in Cav2...
July 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28679634/sec61-blockade-by-mycolactone-inhibits-antigen-cross-presentation-independently-of-endosome-to-cytosol-export
#15
Jeff E Grotzke, Patrycja Kozik, Jean-David Morel, Francis Impens, Natalia Pietrosemoli, Peter Cresswell, Sebastian Amigorena, Caroline Demangel
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD)...
July 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28676924/the-p2x7-receptor
#16
Ronald Sluyter
The P2X7 receptor is a trimeric ion channel gated by extracellular adenosine 5'-triphosphate. The receptor is present on an increasing number of different cells types including stem, blood, glial, neural, ocular, bone, dental, exocrine, endothelial, muscle, renal and skin cells. The P2X7 receptor induces various downstream events in a cell-specific manner, including inflammatory molecule release, cell proliferation and death, metabolic events, and phagocytosis. As such this receptor plays important roles in heath and disease...
July 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28668396/omega-3-fatty-acids-promote-fatty-acid-utilization-and-production-of-pro-resolving-lipid-mediators-in-alternatively-activated-adipose-tissue-macrophages
#17
Martina Rombaldova, Petra Janovska, Jan Kopecky, Ondrej Kuda
It is becoming increasingly apparent that mutual interactions between adipocytes and immune cells are key to the integrated control of adipose tissue inflammation and lipid metabolism in obesity, but little is known about the non-inflammatory functions of adipose tissue macrophages (ATMs) and how they might be impacted by neighboring adipocytes. In the current study we used metabolipidomic analysis to examine the adaptations to lipid overload of M1 or M2 polarized macrophages co-incubated with adipocytes and explored potential benefits of omega-3 polyunsaturated fatty acids (PUFA)...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28651603/a-systems-pharmacology-based-approach-to-identify-novel-kv1-3-channel-dependent-mechanisms-in-microglial-activation
#18
Srikant Rangaraju, Syed Ali Raza, Andrea Pennati, Qiudong Deng, Eric B Dammer, Duc Duong, Michael W Pennington, Malu G Tansey, James J Lah, Ranjita Betarbet, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Kv1.3 potassium channels regulate microglial functions and are overexpressed in neuroinflammatory diseases. Kv1.3 blockade may selectively inhibit pro-inflammatory microglia in neurological diseases but the molecular and cellular mechanisms regulated by Kv1.3 channels are poorly defined. METHODS: We performed immunoblotting and flow cytometry to confirm Kv1.3 channel upregulation in lipopolysaccharide (LPS)-activated BV2 microglia and in brain mononuclear phagocytes freshly isolated from LPS-treated mice...
June 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#19
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#20
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
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