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https://www.readbyqxmd.com/read/28647061/vesicle-fusion-mediated-by-solanesol-anchored-dna
#1
Kristina M Flavier, Steven G Boxer
Fusion between two lipid bilayers is one of the central processes in cell biology, playing a key role in endocytosis, exocytosis, and vesicle transport. We have previously developed a model system that uses the hybridization of complementary DNA strands to model the formation of the SNARE four-helix bundle that mediates synaptic vesicle fusion and used it to study vesicle fusion to a tethered lipid bilayer. Using single vesicle assays, 70% of observed fusion events in the DNA-lipid system are arrested at the hemifusion stage, whereas only 5% eventually go to full fusion...
June 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28645101/co-localization-of-endogenous-arf6-and-its-activator-efa6d-in-the-granular-convoluted-tubule-cells-of-mouse-submandibular-glands-under-normal-conditions-and-when-stimulated-by-isoproterenol-noradrenaline-and-carbachol
#2
Apussara Tachow, Wipawee Thoungseabyoun, Laorrat Phuapittayalert, Kanoktip Petcharat, Hiroyuki Sakagami, Hisatake Kondo, Wiphawi Hipkaeo
OBJECTIVE: This study proposed to investigate the localization at light and electron microscopic levels of Arf6 and its activator EFA6D in the mouse submandibular gland (SMG) under normal conditions and when stimulated by adrenergic or cholinergic agonists. MATERIALS AND METHODS: SMGs of male adult mice were utilized for immunoblotting and immuno-light and -electron microscopic analyses. Isoproterenol and noradrenalin were used as adrenergics, while carbachol was used for the cholinergic stimulant...
June 13, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28640789/complement-mediated-enhancement-of-monocyte-adhesion-to-endothelial-cells-by-hla-antibodies-and-blockade-by-a-specific-inhibitor-of-the-classical-complement-cascade-tnt003
#3
Nicole M Valenzuela, Kimberly A Thomas, Arend Mulder, Graham C Parry, Sandip Panicker, Elaine F Reed
BACKGROUND: Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28638979/endocytosis-is-required-for-exocytosis-and-priming-of-respiratory-burst-activity-in-human-neutrophils
#4
T Michael Creed, Shweta Tandon, Richard A Ward, Kenneth R McLeish
OBJECTIVE AND DESIGN: Neutrophil generation of reactive oxygen species (ROS) is enhanced by exposure to pro-inflammatory agents in a process termed priming. Priming is depending on exocytosis of neutrophil granules and p47(phox) phosphorylation-dependent translocation of cytosolic NADPH oxidase components. Clathrin-mediated endocytosis was recently reported to be necessary for priming, but the mechanism linking endocytosis to priming was not identified. The present study examined the hypothesis that endocytosis regulates neutrophil priming by controlling granule exocytosis...
June 21, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28638403/jaburetox-update-on-a-urease-derived-peptide
#5
REVIEW
Arlete Beatriz Becker-Ritt, Camila Saretta Portugal, Célia Regina Carlini
Urease from Canavalia ensiformis seeds was the first enzyme ever to be crystallized, in 1926. These proteins, found in plants, bacteria and fungi, present different biological properties including catalytic hydrolysis of urea, and also enzyme-independent activities, such as induction of exocytosis, pro-inflammatory effects, neurotoxicity, antifungal and insecticidal properties. Urease is toxic to insects and fungi per se but part of this toxicity relies on an internal peptide (~11 kDa), which is released upon digestion of the protein by insect enzymes...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28634303/structural-characterization-of-the-rabphilin-3a-snap25-interaction
#6
Cristina Ferrer-Orta, María Dolores Pérez-Sánchez, Teresa Coronado-Parra, Cristina Silva, David López-Martínez, Jesús Baltanás-Copado, Juan Carmelo Gómez-Fernández, Senena Corbalán-García, Núria Verdaguer
Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and SNAP25 to bind the plasma membrane, adopting a conformation compatible to interact with the complete SNARE complex...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28632202/genome-wide-association-study-of-borderline-personality-disorder-reveals-genetic-overlap-with-bipolar-disorder-major-depression-and-schizophrenia
#7
S H Witt, F Streit, M Jungkunz, J Frank, S Awasthi, C S Reinbold, J Treutlein, F Degenhardt, A J Forstner, S Heilmann-Heimbach, L Dietl, C E Schwarze, D Schendel, J Strohmaier, A Abdellaoui, R Adolfsson, T M Air, H Akil, M Alda, N Alliey-Rodriguez, O A Andreassen, G Babadjanova, N J Bass, M Bauer, B T Baune, F Bellivier, S Bergen, A Bethell, J M Biernacka, D H R Blackwood, M P Boks, D I Boomsma, A D Børglum, M Borrmann-Hassenbach, P Brennan, M Budde, H N Buttenschøn, E M Byrne, P Cervantes, T-K Clarke, N Craddock, C Cruceanu, D Curtis, P M Czerski, U Dannlowski, T Davis, E J C de Geus, A Di Florio, S Djurovic, E Domenici, H J Edenberg, B Etain, S B Fischer, L Forty, C Fraser, M A Frye, J M Fullerton, K Gade, E S Gershon, I Giegling, S D Gordon, K Gordon-Smith, H J Grabe, E K Green, T A Greenwood, M Grigoroiu-Serbanescu, J Guzman-Parra, L S Hall, M Hamshere, J Hauser, M Hautzinger, U Heilbronner, S Herms, S Hitturlingappa, P Hoffmann, P Holmans, J-J Hottenga, S Jamain, I Jones, L A Jones, A Juréus, R S Kahn, J Kammerer-Ciernioch, G Kirov, S Kittel-Schneider, S Kloiber, S V Knott, M Kogevinas, M Landén, M Leber, M Leboyer, Q S Li, J Lissowska, S Lucae, N G Martin, F Mayoral-Cleries, S L McElroy, A M McIntosh, J D McKay, A McQuillin, S E Medland, C M Middeldorp, Y Milaneschi, P B Mitchell, G W Montgomery, G Morken, O Mors, T W Mühleisen, B Müller-Myhsok, R M Myers, C M Nievergelt, J I Nurnberger, M C O'Donovan, L M O Loohuis, R Ophoff, L Oruc, M J Owen, S A Paciga, B W J H Penninx, A Perry, A Pfennig, J B Potash, M Preisig, A Reif, F Rivas, G A Rouleau, P R Schofield, T G Schulze, M Schwarz, L Scott, G C B Sinnamon, E A Stahl, J Strauss, G Turecki, S Van der Auwera, H Vedder, J B Vincent, G Willemsen, C C Witt, N R Wray, H S Xi, A Tadic, N Dahmen, B H Schott, S Cichon, M M Nöthen, S Ripke, A Mobascher, D Rujescu, K Lieb, S Roepke, C Schmahl, M Bohus, M Rietschel
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28626002/ride-the-wave-retrograde-trafficking-becomes-ca-2-dependent-with-baiap3
#8
Jakob B Sørensen
The functions of four of the five proteins in the mammalian uncoordinated-13 (Munc13) family have been identified as priming factors in SNARE-dependent exocytosis. In this issue, Zhang et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201702099) show that the fifth member, BAIAP3 (brain-specific angiogenesis inhibitor I-associated protein 3), acts in retrograde trafficking by returning secretory vesicle material to the trans-Golgi network. In its absence, secretory vesicle formation is impaired, leading to accumulation of immature vesicles, or lysosomal vesicle degradation...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28626000/baiap3-a-c2-domain-containing-munc13-protein-controls-the-fate-of-dense-core-vesicles-in-neuroendocrine-cells
#9
Xingmin Zhang, Shan Jiang, Kelly A Mitok, Lingjun Li, Alan D Attie, Thomas F J Martin
Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca(2+)-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain-containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#10
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/28611952/multiple-phenotypic-changes-define-neutrophil-priming
#11
REVIEW
Irina Miralda, Silvia M Uriarte, Kenneth R McLeish
Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28607108/kv2-1-clustering-contributes-to-insulin-exocytosis-and-rescues-human-%C3%AE-cell-dysfunction
#12
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...
June 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28600434/concerted-actions-of-distinct-nonmuscle-myosin-ii-isoforms-drive-intracellular-membrane-remodeling-in-live-animals
#13
Oleg Milberg, Akiko Shitara, Seham Ebrahim, Andrius Masedunskas, Muhibullah Tora, Duy T Tran, Yun Chen, Mary Anne Conti, Robert S Adelstein, Kelly G Ten Hagen, Roberto Weigert
Membrane remodeling plays a fundamental role during a variety of biological events. However, the dynamics and the molecular mechanisms regulating this process within cells in mammalian tissues in situ remain largely unknown. In this study, we use intravital subcellular microscopy in live mice to study the role of the actomyosin cytoskeleton in driving the remodeling of membranes of large secretory granules, which are integrated into the plasma membrane during regulated exocytosis. We show that two isoforms of nonmuscle myosin II, NMIIA and NMIIB, control distinct steps of the integration process...
June 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28596722/unique-structural-features-of-membrane-bound-c-terminal-domain-motifs-modulate-complexin-inhibitory-function
#14
David Snead, Alex L Lai, Rachel T Wragg, Daniel A Parisotto, Trudy F Ramlall, Jeremy S Dittman, Jack H Freed, David Eliezer
Complexin is a small soluble presynaptic protein that interacts with neuronal SNARE proteins in order to regulate synaptic vesicle exocytosis. While the SNARE-binding central helix of complexin is required for both the inhibition of spontaneous fusion and the facilitation of synchronous fusion, the disordered C-terminal domain (CTD) of complexin is specifically required for its inhibitory function. The CTD of worm complexin binds to membranes via two distinct motifs, one of which undergoes a membrane curvature dependent structural transition that is required for efficient inhibition of neurotransmitter release, but the conformations of the membrane-bound motifs remain poorly characterized...
2017: Frontiers in Molecular Neuroscience
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
#15
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/28591730/downregulation-of-serum-rab27b-confers-improved-prognosis-and-is-associated-with-hepatocellular-carcinoma-progression-through-pi3k-akt-p21-signaling
#16
Xue Yang, Xieqiong Ye, Le Sun, Fangyuan Gao, Yuxin Li, Xiaomin Ji, Xuejiang Wang, Ying Feng, Xianbo Wang
Previous study revealed that elevated expression of RAB27B in tissues is correlated with hepatocellular carcinoma (HCC) progression; however, the mechanisms involved in promoting HCC development are still unclear. Moreover, HCC tissues are not readily obtained during routine diagnosis. Therefore, to further explore its potential value in early diagnosis, we examined RAB27B expression in patient sera. First, the correlation between serum RAB27B expression and survival, as well as TNM and Barcelona Clinic Liver Cancer stages, were evaluated in patients with HCC...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588281/a-central-small-amino-acid-in-the-vamp2-transmembrane-domain-regulates-the-fusion-pore-in-exocytosis
#17
Benoît Hastoy, Pier A Scotti, Alexandra Milochau, Zahia Fezoua-Boubegtiten, Jorge Rodas, Rémi Megret, Bernard Desbat, Michel Laguerre, Sabine Castano, David Perrais, Patrik Rorsman, Reiko Oda, Jochen Lang
Exocytosis depends on cytosolic domains of SNARE proteins but the function of the transmembrane domains (TMDs) in membrane fusion remains controversial. The TMD of the SNARE protein synaptobrevin2/VAMP2 contains two highly conserved small amino acids, G100 and C103, in its central portion. Substituting G100 and/or C103 with the β-branched amino acid valine impairs the structural flexibility of the TMD in terms of α-helix/β-sheet transitions in model membranes (measured by infrared reflection-absorption or evanescent wave spectroscopy) during increase in protein/lipid ratios, a parameter expected to be altered by recruitment of SNAREs at fusion sites...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586379/lamp-2-absence-interferes-with-plasma-membrane-repair-and-decreases-t-cruzi-host-cell-invasion
#18
Natália Fernanda Couto, Dina Pedersane, Luisa Rezende, Patrícia P Dias, Tayanne L Corbani, Lívia C Bentini, Anny C S Oliveira, Ludmila F Kelles, Thiago Castro-Gomes, Luciana O Andrade
Trypanosoma cruzi enters host cells by subverting the mechanism of cell membrane repair. In this process, the parasite induces small injuries in the host cell membrane leading to calcium entry and lysosomal exocytosis, which are followed by compensatory endocytosis events that drive parasites into host cells. We have previously shown that absence of both LAMP-1 and 2, major components of lysosomal membranes, decreases invasion of T. cruzi into host cells, but the mechanism by which they interfere with parasite invasion has not been described...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28585545/sox5-regulates-beta-cell-phenotype-and-is-reduced-in-type-2-diabetes
#19
A S Axelsson, T Mahdi, H A Nenonen, T Singh, S Hänzelmann, A Wendt, A Bagge, T M Reinbothe, J Millstein, X Yang, B Zhang, E G Gusmao, L Shu, M Szabat, Y Tang, J Wang, S Salö, L Eliasson, I Artner, M Fex, J D Johnson, C B Wollheim, J M J Derry, B Mecham, P Spégel, H Mulder, I G Costa, E Zhang, A H Rosengren
Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca(2+)-influx and β-cell exocytosis...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28580284/nnt-reverse-mode-of-operation-mediates-glucose-control-of-mitochondrial-nadph-and-glutathione-redox-state-in-mouse-pancreatic-%C3%AE-cells
#20
Laila R B Santos, Carole Muller, Arnaldo H de Souza, Hilton K Takahashi, Peter Spégel, Ian R Sweet, Heeyoung Chae, Hindrik Mulder, Jean-Christophe Jonas
OBJECTIVE: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca(2+) influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets...
June 2017: Molecular Metabolism
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