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https://www.readbyqxmd.com/read/28325894/sumoylation-and-calcium-control-syntaxin-1a-and-secretagogin-sequestration-by-tomosyn-to-regulate-insulin-exocytosis-in-human-%C3%A3-cells
#1
Mourad Ferdaoussi, Jianyang Fu, Xiaoqing Dai, Jocelyn E Manning Fox, Kunimasa Suzuki, Nancy Smith, Gregory Plummer, Patrick E MacDonald
Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca(2+). Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca(2+)-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca(2+)-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca(2+) influx...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314963/mir-124a-expression-contributes-to-the-monophasic-pattern-of-insulin-secretion-in-islets-from-pregnant-rats-submitted-to-a-low-protein-diet
#2
Kariny Cassia de Siqueira, Faena Moura de Lima, Fernanda Souza Lima, Marina Satie Taki, Clarissa Felfili da Cunha, Sílvia Regina de Lima Reis, Rafael Ludemann Camargo, Thiago Martins Batista, Emerielle Cristine Vanzela, Tarlliza Romanna Nardelli, Everardo Magalhães Carneiro, Silvana Bordin, Letícia Martins Ignácio-Souza, Márcia Queiroz Latorraca
PURPOSE: To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet. METHODS: Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy...
March 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28265073/sm-protein-munc18-2-facilitates-transition-of-syntaxin-11-mediated-lipid-mixing-to-complete-fusion-for-t-lymphocyte-cytotoxicity
#3
Waldo A Spessott, Maria L Sanmillan, Margaret E McCormick, Vineet V Kulkarni, Claudio G Giraudo
The atypical lipid-anchored Syntaxin 11 (STX11) and its binding partner, the Sec/Munc (SM) protein Munc18-2, facilitate cytolytic granule release by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Patients carrying mutations in these genes develop familial hemophagocytic lymphohistiocytosis, a primary immunodeficiency characterized by impaired lytic granule exocytosis. However, whether a SNARE such as STX11, which lacks a transmembrane domain, can support membrane fusion in vivo is uncertain, as is the precise role of Munc18-2 during lytic granule exocytosis...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202687/oxidized-phagosomal-nox2-is-replenished-from-lysosomes
#4
Ilse Dingjan, Peter T A Linders, Luuk van den Bekerom, Maksim V Baranov, Partho Halder, Martin Ter Beest, Geert van den Bogaart
In dendritic cells, the NADPH oxidase 2 (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome which kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b558, traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b558 is initially recruited to the phagosome from the plasma membrane during phagosome formation...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28202235/stx12-lncrna-mir-148a-smad5-participate-in-the-regulation-of-pancreatic-stellate-cell-activation-through-a-mechanism-involving-competing-endogenous-rna
#5
Hao Wang, Yanfeng Jiang, Ming Lu, Bei Sun, Xin Qiao, Dongbo Xue, Weihui Zhang
BACKGROUND: With the deepening of research, the roles of LncRNAs play in the fibrotic process have attracted great attention. At the early stage of pancreatic fibrogenesis, to effectively regulate pancreatic stellate cells (PSCs) activation is crucial for the treatment of chronic pancreatic fibrosis. METHODS: Microarray data on chronic pancreatitis were retrieved from the Gene Expression Omnibus (GEO) repository and analyzed using bioinformatic methods. A diagram of the lncRNA-miRNA-mRNA ceRNA network was constructed...
February 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28163686/the-multifaceted-role-of-snare-proteins-in-membrane-fusion
#6
REVIEW
Jing Han, Kristyna Pluhackova, Rainer A Böckmann
Membrane fusion is a key process in all living organisms that contributes to a variety of biological processes including viral infection, cell fertilization, as well as intracellular transport, and neurotransmitter release. In particular, the various membrane-enclosed compartments in eukaryotic cells need to exchange their contents and communicate across membranes. Efficient and controllable fusion of biological membranes is known to be driven by cooperative action of SNARE proteins, which constitute the central components of the eukaryotic fusion machinery responsible for fusion of synaptic vesicles with the plasma membrane...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28163042/munc18b-increases-insulin-granule-fusion-restoring-deficient-insulin-secretion-in-type-2-diabetes-human-and-goto-kakizaki-rat-islets-with-improvement-in-glucose-homeostasis
#7
Tairan Qin, Tao Liang, Dan Zhu, Youhou Kang, Li Xie, Subhankar Dolai, Shuzo Sugita, Noriko Takahashi, Claes-Goran Ostenson, Kate Banks, Herbert Y Gaisano
Reduced pancreatic islet levels of Munc18a/SNARE complex proteins have been postulated to contribute to the deficient glucose-stimulated insulin secretion (GSIS) in type-2 diabetes (T2D). Whereas much previous work has purported Munc18a/SNARE complex (Syntaxin-1A/VAMP-2/SNAP25) to be primarily involved in predocked secretory granule (SG) fusion, less is known about newcomer SGs that undergo minimal docking time at the plasma membrane before fusion. Newcomer SG fusion has been postulated to involve a distinct SM/SNARE complex (Munc18b/Syntaxin-3/VAMP8/SNAP25), whose levels we find also reduced in islets of T2D humans and T2D Goto-Kakizaki (GK) rats...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28137749/conformational-change-of-syntaxin-linker-region-induced-by-munc13s-initiates-snare-complex-formation-in-synaptic-exocytosis
#8
Shen Wang, Ucheor B Choi, Jihong Gong, Xiaoyu Yang, Yun Li, Austin L Wang, Xiaofei Yang, Axel T Brunger, Cong Ma
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1 adopts a closed conformation when bound to Munc18-1, preventing binding to synaptobrevin-2 and SNAP-25 to form the ternary SNARE complex. Although it is known that the MUN domain of Munc13-1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular mechanism is unclear. Here, we identified two conserved residues (R151, I155) in the syntaxin-1 linker region as key sites for the MUN domain interaction...
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28119011/syntaxin-4-and-snap23-act-as-exocytic-snares-to-release-ngf-from-cultured-schwann-cells
#9
Mengsi Lin, Maorong Jiang, Fei Ding, Zheng Cao
Nowadays peripheral nerve (PN) injury occurs more frequently, the outcome is often poor because of the ineffective treatment. Once the PN was injured, Schwann cells (SCs) release neurotrophins to guide the regeneration of axons. Recent researches revealed the duration of NGF administration acts a positive role during the nerve regeneration, but the molecular mechanisms of NGF release from SCs are unknown. To investigate components of the exocytic machinery of NGF, we used RT-PCR, Western blot and immunocytochemistry to investigate expressions and locations of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in rat primary cultured SCs...
January 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28116546/cortical-synaptic-transmission-and-plasticity-in-acute-liver-failure-are-decreased-by-presynaptic-events
#10
Mariusz Popek, Bartosz Bobula, Joanna Sowa, Grzegorz Hess, Rafał Polowy, Robert Kuba Filipkowski, Małgorzata Frontczak-Baniewicz, Barbara Zabłocka, Jan Albrecht, Magdalena Zielińska
Neurological symptoms of acute liver failure (ALF) reflect decreased excitatory transmission, but the status of ALF-affected excitatory synapse has not been characterized in detail. We studied the effects of ALF in mouse on synaptic transmission and plasticity ex vivo and its relation to distribution of (i) synaptic vesicles (sv) and (ii) functional synaptic proteins within the synapse. ALF-competent neurological and biochemical changes were induced in mice with azoxymethane (AOM). Electrophysiological characteristics (long-term potentiation, whole-cell recording) as well as synapse ultrastructure were evaluated in the cerebral cortex...
January 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28115395/syntaxin-2-acts-as-inhibitory-snare-for-insulin-granule-exocytosis
#11
Dan Zhu, Li Xie, Youhou Kang, Subhankar Dolai, Jakob Bondo Hansen, Tairan Qin, Huanli Xie, Tao Liang, Deborah C Rubin, Lucy Osborne, Herbert Y Gaisano
Of the four syntaxins (Syns) specialized for exocytosis, syntaxin-2 is the least understood. Here, we employed syntaxin-2/epimorphin knockout (KO) mice to examine the role of syntaxin-2 in insulin secretory granule (SG) exocytosis. Unexpectedly, syntaxin-2 KO mice exhibited paradoxical superior glucose homeostasis resulting from an enhanced insulin secretion. This was confirmed in vitro by pancreatic islet perifusion showing an amplified biphasic glucose-stimulated insulin secretion (GSIS) arising from an increase in size of the readily-releasable pool of insulin SGs and enhanced SG pool refilling...
January 23, 2017: Diabetes
https://www.readbyqxmd.com/read/28104350/neonatal-exposure-to-bde-209-impaired-learning-and-memory-decreased-expression-of-hippocampal-core-snares-and-synaptophysin-in-adult-rats
#12
Xiong Li, Chunmei Wang, Wen Wang, Chengwei Yue, Yan Tang
Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants. While the mechanism remains unknown, the potential neurotoxic effects of PBDEs remain a relevant issue. In the present study, neonatal Sprague-Dawley rats of both sexes were administered BDE 209 (1, 10, or 20mg/kg body weight) or peanut oil once daily from postnatal day (PND) 5 to PND 10. We examined the spatial learning and memory by Morris water maze and the working and reference memory by eight-arm radial maze in the stage of adulthood...
January 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28087642/stxbp4-drives-tumor-growth-and-is-associated-with-poor-prognosis-through-pdgf-receptor-signaling-in-lung-squamous-cell-carcinoma
#13
Yukihiro Otaka, Susumu Rokudai, Kyoichi Kaira, Michiru Fujieda, Ikuko Horikoshi, Reika Kawabata, Shinji Yoshiyama, Takehiko Yokobori, Yoichi Ohtaki, Kimihiro Shimizu, Tetsunari Oyama, Jun'ichi Tamura, Carol Prives, Masahiko Nishiyama
PURPOSE: Expression of the ΔN isoform of p63 (ΔNp63) is a diagnostic marker highly specific for lung squamous cell carcinoma (SCC). We previously found that Syntaxin Binding Protein 4 (STXBP4) regulates ΔNp63 ubiquitination, suggesting that STXBP4 may also be a SCC biomarker. To address this issue, we investigated the role of STXBP4 expression in SCC biology and the impact of STXBP4 expression on SCC prognosis. EXPERIMENTAL DESIGN: We carried out a clinicopathological analysis of STXBP4 expression in 87 lung SCC patients...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28057922/membrane-translocation-of-t-snare-protein-syntaxin-4-abrogates-ground-state-pluripotency-in-mouse-embryonic-stem-cells
#14
Natsumi Hagiwara-Chatani, Kota Shirai, Takumi Kido, Tomoatsu Horigome, Akihiro Yasue, Naoki Adachi, Yohei Hirai
Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28034831/protein-disulfide-isomerase-externalization-in-endothelial-cells-follows-classical-and-unconventional-routes
#15
Thaís L S Araujo, Julianna D Zeidler, Percíllia V S Oliveira, Matheus H Dias, Hugo A Armelin, Francisco R M Laurindo
Extracellular protein disulfide isomerase (PDIA1) pool mediates thrombosis and vascular remodeling, however its externalization mechanisms remain unclear. We performed systematic pharmacological screening of secretory pathways affecting extracellular PDIA1 in endothelial cells (EC). We identified cell-surface (csPDIA1) and secreted non-particulated PDIA1 pools in EC. Such Golgi bypass also occurred for secreted PDIA1 in EC at baseline or after PMA, thrombin or ATP stimulation. Inhibitors of Type I, II and III unconventional routes, secretory lysosomes and recycling endosomes, including syntaxin-12 deletion, did not impair EC PDIA1 externalization...
December 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28033683/snare-proteins-play-a-role-in-motor-axon-guidance-in-vertebrates-and-invertebrates
#16
Pablo José Barrecheguren, Oriol Ros, Tiziana Cotrufo, Beat Kunz, Eduardo Soriano, Fausto Ulloa, Esther T Stoeckli, Sofia J Araújo
Axonal growth and guidance rely on correct growth cone responses to guidance cues, both in the central nervous system (CNS) and in the periphery. Unlike the signaling cascades that link axonal growth to cytoskeletal dynamics, little is known about the crosstalk mechanisms between guidance and membrane dynamics and turnover in the axon. Our studies have shown that Netrin-1/Deleted in Colorectal Cancer (DCC) signaling triggers exocytosis through the SNARE Syntaxin-1 (STX-1) during the formation of commissural pathways...
December 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/28031464/new-roles-of-syntaxin-1a-in-insulin-granule-exocytosis-and-replenishment
#17
Tao Liang, Tairan Qin, Li Xie, Subhankar Dolai, Dan Zhu, Kacey J Prentice, Michael Wheeler, Youhou Kang, Lucy Osborne, Herbert Y Gaisano
In type-2 diabetes (T2D), severely reduced islet syntaxin-1A (Syn-1A) levels contribute to insulin secretory deficiency. We generated β-cell-specific Syn-1A-KO (Syn-1A-βKO) mice to mimic β-cell Syn-1A deficiency in T2D. Glucose tolerance tests showed that Syn-1A-βKO mice exhibited blood glucose elevation corresponding to reduced blood insulin levels. Perifusion of Syn-1A-βKO islets showed impaired first- and second-phase glucose-stimulated insulin secretion (GSIS) resulting from reduction in readily releasable pool and granule pool refilling...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28010187/components-of-the-snare-containing-regulon-are-co-regulated-in-root-cells-undergoing-defense
#18
Vincent P Klink, Keshav Sharma, Shankar R Pant, Brant McNeece, Prakash Niraula, Gary W Lawrence
The term regulon has been coined in the genetic model plant Arabidopsis thaliana, denoting a structural and physiological defense apparatus defined genetically through the identification of the penetration (pen) mutants. The regulon is composed partially by the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) syntaxin PEN1. PEN1 has homology to a Saccharomyces cerevisae gene that regulates a Secretion (Sec) protein, Suppressor of Sec 1 (Sso1p). The regulon is also composed of the β-glucosidase (PEN2) and an ATP binding cassette (ABC) transporter (PEN3)...
February 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28000760/mice-lacking-wrb-reveal-differential-biogenesis-requirements-of-tail-anchored-proteins-in-vivo
#19
Jhon Rivera-Monroy, Lena Musiol, Kirsten Unthan-Fechner, Ákos Farkas, Anne Clancy, Javier Coy-Vergara, Uri Weill, Sarah Gockel, Shuh-Yow Lin, David P Corey, Tobias Kohl, Philipp Ströbel, Maya Schuldiner, Blanche Schwappach, Fabio Vilardi
Tail-anchored (TA) proteins are post-translationally inserted into membranes. The TRC40 pathway targets TA proteins to the endoplasmic reticulum via a receptor comprised of WRB and CAML. TRC40 pathway clients have been identified using in vitro assays, however, the relevance of the TRC40 pathway in vivo remains unknown. We followed the fate of TA proteins in two tissue-specific WRB knockout mouse models and found that their dependence on the TRC40 pathway in vitro did not predict their reaction to receptor depletion in vivo...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27988858/sequence-specific-assignment-of-methyl-groups-from-the-neuronal-snare-complex-using-lanthanide-induced-pseudocontact-shifts
#20
Yun-Zu Pan, Bradley Quade, Kyle D Brewer, Monika Szabo, James D Swarbrick, Bim Graham, Josep Rizo
Neurotransmitter release depends critically on the neuronal SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin, as well as on other proteins such as Munc18-1, Munc13-1 and synaptotagmin-1. Although three-dimensional structures are available for these components, it is still unclear how they are assembled between the synaptic vesicle and plasma membranes to trigger fast, Ca(2+)-dependent membrane fusion. Methyl TROSY NMR experiments provide a powerful tool to study complexes between these proteins, but assignment of the methyl groups of the SNARE complex is hindered by its limited solubility...
December 2016: Journal of Biomolecular NMR
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