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https://www.readbyqxmd.com/read/28815213/identification-of-rab18-as-an-essential-host-factor-for-bk-polyomavirus-infection-using-a-whole-genome-rna-interference-screen
#1
Linbo Zhao, Michael J Imperiale
BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins...
July 2017: MSphere
https://www.readbyqxmd.com/read/28814500/mono-ubiquitination-of-syntaxin-3-leads-to-retrieval-from-the-basolateral-plasma-membrane-and-facilitates-cargo-recruitment-to-exosomes
#2
Adrian J Giovannone, Elena Reales, Pallavi Bhattaram, Alberto Fraile-Ramos, Thomas Weimbs
Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes though how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes mono-ubiquitination in a conserved polybasic domain. Stx3 present at the basolateral - but not the apical - plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs) and excreted in exosomes...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#3
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28772123/molecular-mechanisms-of-synaptic-vesicle-priming-by-munc13-and-munc18
#4
Ying Lai, Ucheor B Choi, Jeremy Leitz, Hong Jun Rhee, Choongku Lee, Bekir Altas, Minglei Zhao, Richard A Pfuetzner, Austin L Wang, Nils Brose, JeongSeop Rhee, Axel T Brunger
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca(2+)-triggered amplitude and achieves Ca(2+) sensitivity at near-physiological concentrations...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#5
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28753981/a-membrane-fusion-model-that-exploits-a-%C3%AE-to-%C3%AE-transition-in-the-hydrophobic-domains-of-syntaxin-1a-and-synaptobrevin-2
#6
Cameron B Gundersen
Parallel zippering of the SNARE domains of syntaxin 1A/B, SNAP-25, and VAMP/synaptobrevin 2 is widely regarded as supplying the driving force for exocytotic events at nerve terminals and elsewhere. However, in spite of intensive research, no consensus has been reached concerning the molecular mechanism by which these SNARE proteins catalyze membrane fusion. As an alternative to SNARE-based models, a scenario was developed in which synaptotagmin 1 (or, 2) can serve as a template to guide lipid movements that underlie fast, synchronous exocytosis at nerve terminals...
July 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28722652/the-packing-density-of-a-supramolecular-membrane-protein-cluster-is-controlled-by-cytoplasmic-interactions
#7
Elisa Merklinger, Jan-Gero Schloetel, Pascal Weber, Helena Batoulis, Sarah Holz, Nora Karnowski, Jérôme Finke, Thorsten Lang
Molecule clustering is an important mechanism underlying cellular self-organization. In the cell membrane, a variety of fundamentally different mechanisms drive membrane protein clustering into nanometre-sized assemblies. To date, it is unknown whether this clustering process can be dissected into steps differentially regulated by independent mechanisms. Using clustered syntaxin molecules as an example, we study the influence of a cytoplasmic protein domain on the clustering behaviour. Analysing protein mobility, cluster size and accessibility to myc-epitopes we show that forces acting on the transmembrane segment produce loose clusters, while cytoplasmic protein interactions mediate a tightly packed state...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28692549/a-case-of-familial-hemophagocytic-lymphohistiocytosis-type-4-with-involvement-of-the-central-nervous-system-complicated-with-infarct
#8
Saliha Ciraci, Alper Ozcan, Mustafa M Ozdemir, Samuel C C Chiang, Bianca Tesi, Akif M Ozdemir, Musa Karakukcu, Turkan Patiroglu, Can Acipayam, Selim Doganay, Hakan Gumus, Ekrem Unal
BACKGROUND: Familial hemophagocytic lymphohistiocytosis (HLH) is a fatal disease affecting infants and very young children. Central nervous system involvement of HLH can cause catastrophic results. METHOD: We present a case with cranial involvement of familial HLH type 4 who showed diffuse infiltration of white matter complicated with intracranial thrombosis. A 5-year-old girl from a consanguineous couple presented with fever and pancytopenia, and was referred to our hematology unit...
July 7, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28677644/2bc-non-structural-protein-of-enterovirus-a71-interacts-with-snare-proteins-to-trigger-autolysosome-formation
#9
Jeffrey K F Lai, I-Ching Sam, Pauline Verlhac, Joël Baguet, Eeva-Liisa Eskelinen, Mathias Faure, Yoke Fun Chan
Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation...
July 4, 2017: Viruses
https://www.readbyqxmd.com/read/28642677/a-novel-workflow-combining-plaque-imaging-plaque-and-plasma-proteomics-identifies-biomarkers-of-human-coronary-atherosclerotic-plaque-disruption
#10
Regent Lee, Roman Fischer, Philip D Charles, David Adlam, Alessandro Valli, Katalin Di Gleria, Rajesh K Kharbanda, Robin P Choudhury, Charalambos Antoniades, Benedikt M Kessler, Keith M Channon
BACKGROUND: Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#11
Mingfeng Zhuang, Bingwei Sun, Dadong Liu, Yuan Shi
OBJECTIVE: To investigate the suppressive effect of carbon monoxide-releasing molecule II (CORM-2) on LPS induced platelet α-granule exocytosis in sepsis via soluble N-ethylmaleimide-sensitive factor attached protein receptor/mammalian uncoordinated 18b (SNARE/Munc18b) complex formation. METHODS: Blood was collected from healthy volunteers' cubital vein, then platelets were isolated by differential centrifugation. Platelets were randomly divided into 5 groups. The control group did not undergo any treatment, the LPS group received 10 mg/L LPS simulation, the CORM-2 group and iCORM-2 group underwent LPS simulation and immediate administration of CORM-2 (10 μmol/L and 50 μmol/L) or iCORM-2 (50 μmol/L), respectively...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28624237/identification-of-syntaxin-4-as-an-essential-factor-for-the-hepatitis-c-virus-life-cycle
#12
Huimei Ren, Fabian Elgner, Kiyoshi Himmelsbach, Sami Akhras, Bingfu Jiang, Regina Medvedev, Daniela Ploen, Eberhard Hildt
Although there is evidence that multivesicular bodies (MVBs) are involved in the release of hepatitis C virus (HCV), many aspects of HCV release are still not fully understood. The amount of α-taxilin that prevents SNARE (soluble N-ethylmaleimidesensitive factor attachment protein receptor) complex formation by binding to free syntaxin 4 is reduced in HCV-positive cells. Therefore, it was analyzed whether the t-SNARE protein syntaxin 4 which mediates vesicles fusion is involved in the HCV life cycle. HCV-positive cells possess an increased amount of syntaxin 4 protein, although the amount of syntaxin 4-specific transcripts is decreased in HCV-positive Huh7...
June 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#13
Farr Niere, Kimberly F Raab-Graham
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28607108/kv2-1-clustering-contributes-to-insulin-exocytosis-and-rescues-human-%C3%AE-cell-dysfunction
#14
Jianyang Fu, Xiaoqing Dai, Gregory Plummer, Kunimasa Suzuki, Austin Bautista, John M Githaka, Laura Senior, Mette Jensen, Dafna Greitzer-Antes, Jocelyn E Manning Fox, Herbert Y Gaisano, Christopher B Newgard, Nicolas Touret, Patrick E MacDonald
Insulin exocytosis is regulated by ion channels that control excitability and Ca(2+) influx. Channels also play an increasingly appreciated role in microdomain structure. In this study, we examine the mechanism by which the voltage-dependent K(+) (Kv) channel Kv2.1 (KCNB1) facilitates depolarization-induced exocytosis in INS 832/13 cells and β-cells from human donors with and without type 2 diabetes (T2D). We find that Kv2.1, but not Kv2.2 (KCNB2), forms clusters of 6-12 tetrameric channels at the plasma membrane and facilitates insulin exocytosis...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28598244/accumulation-of-undegraded-autophagosomes-by-expression-of-dominant-negative-stx17-syntaxin-17-mutants
#15
Masaaki Uematsu, Taki Nishimura, Yuriko Sakamaki, Hayashi Yamamoto, Noboru Mizushima
Macroautophagy/autophagy, which is one of the main degradation systems in the cell, is mediated by a specialized organelle, the autophagosome. Purification of autophagosomes before fusion with lysosomes is important for both mechanistic and physiological studies of the autophagosome. Here, we report a simple method to accumulate undigested autophagosomes. Overexpression of the autophagosomal Qa-SNARE STX17 (syntaxin 17) lacking the N-terminal domain (NTD) or N-terminally tagged GFP-STX17 causes accumulation of autophagosomes...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28596237/the-snare-protein-syntaxin1a-plays-an-essential-role-in-biphasic-exocytosis-of-the-incretin-hormone-glucagon-like-peptide-1
#16
Sarah E Wheeler, Holly M Stacey, Yasaman Nahaei, Stephen J Hale, Alexandre B Hardy, Frank Reimann, Fiona M Gribble, Pierre Larraufie, Herbert Y Gaisano, Patricia L Brubaker
Exocytosis of the hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is essential for the incretin effect after nutrient ingestion, and is critical for the actions of dipeptidylpeptidase IV inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. 2-Photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a 1(st) peak at 1-6min and a 2(nd) peak at 7-12min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules, under basal and stimulated conditions...
June 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28593826/exposure-to-static-magnetic-fields-increases-insulin-secretion-in-rat-ins-1-cells-by-activating-the-transcription-of-the-insulin-gene-and-up-regulating-the-expression-of-vesicle-secreted-proteins
#17
Libin Mao, Huiqin Wang, Fenghui Ma, Zhixia Guo, Hongpeng He, Hao Zhou, Nan Wang
PURPOSE: To evaluate the effect of static magnetic fields (SMFs) on insulin secretion and explore the mechanisms underlying exposure to SMF-induced insulin secretion in rat insulinoma INS-1 cells. MATERIALS AND METHODS: INS-1 cells were exposed to a 400 mT SMF for 72 h, and the proliferation of INS-1 cells was detected by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The secretion of insulin was measured with an enzyme linked immunosorbent assays (ELISA), the expression of genes was detected by real-time PCR, and the expression of proteins was measured by Western blotting...
June 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28579390/fluorescent-markers-of-various-organelles-in-the-wheat-pathogen-zymoseptoria-tritici
#18
S Kilaru, M Schuster, W Ma, G Steinberg
Development of novel strategies to control fungal plant pathogens requires understanding of their cellular organisation and biology. Live cell imaging of fluorescent organelle markers has provided valuable insight into various aspects of their cell biology, including invasion strategies in plant pathogenic fungi. Here, we introduce a set of 17 vectors that encode fluorescent markers to visualize the plasma membrane, endoplasmic reticulum (ER), chromosomes, the actin cytoskeleton, peroxisomes and autophagosomes in the wheat pathogen Zymoseptoria tritici...
August 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28560580/pmicrorna-124a-regulates-lps-induced-septic-cardiac-dysfunction-by-targeting-stx2
#19
Xiufang Diao, Shuqing Sun
OBJECTIVE: To examine the role of miR-124a in LPS-induced septic cardiac insufficiency where underlying mechanism is unclear. RESULTS: Expression of miR-124a was decreased in myocardium of LPS-induced septic cardiac dysfunction model. miR-124a antagomiR or agomiR were injected via tail vein to induce miR-124a-dysregulated model. miR-124a antagomiR aggravated LPS-induced cardiac dysfunction and apoptosis, while miR-124a agomiR had the opposite effect. Syntaxin-2 (STX2) was indicated as a candidate target gene by bioinformatic software...
May 30, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28559542/march9-mediated-ubiquitination-regulates-mhc-i-export-from-the-tgn
#20
Francesca De Angelis Rigotti, Aude De Gassart, Carina Pforr, Florencia Cano, Prudence N'Guessan, Alexis Combes, Voahirana Camossetto, Paul Lehner, Philippe Pierre, Evelina Gatti
Given the heterogeneous nature of antigens, MHC-I intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC-I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC-I delivery to the plasma membrane. We show here that MHC-I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues...
May 31, 2017: Immunology and Cell Biology
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