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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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(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 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...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28010187/components-of-the-snare-containing-regulon-are-co-regulated-in-root-cells-undergoing-defense
#7
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)...
December 23, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28000760/mice-lacking-wrb-reveal-differential-biogenesis-requirements-of-tail-anchored-proteins-in-vivo
#8
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
#9
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
https://www.readbyqxmd.com/read/27984133/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#10
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
October 29, 2016: Toxicology
https://www.readbyqxmd.com/read/27974193/perinatal-exposure-to-lead-pb-induces-ultrastructural-and-molecular-alterations-in-synapses-of-rat-offspring
#11
Magdalena Gąssowska, Irena Baranowska-Bosiacka, Joanna Moczydłowska, Małgorzata Frontczak-Baniewicz, Magdalena Gewartowska, Lidia Strużyńska, Izabela Gutowska, Dariusz Chlubek, Agata Adamczyk
Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27933643/syntaxin-4a-regulates-matrix-vesicle-mediated-bone-matrix-production-by-osteoblasts
#12
Shinji Kawai, Ikumi Michikami, Jirouta Kitagaki, Kenji Hata, Hiroshi Kiyonari, Takaya Abe, Atsuo Amano, Satoshi Wakisaka
Osteoblasts secrete matrix vesicles and proteins to bone surfaces, though the molecular mechanisms of this secretion system remain unclear. The present findings reveal the roles of important genes in osteoblasts involved in regulation of extracellular matrix secretion. We especially focused on SNARE genes and identified notable Syntaxin 4a (Stx4a) expression on the basolateral side of the plasma membrane of osteoblasts. Furthermore, Stx4a overexpression was found to increase mineralization by osteoblastic cells, whereas Stx4a knockdown reduced levels of mineralization...
December 8, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27932448/dedicated-snares-and-specialized-trim-cargo-receptors-mediate-secretory-autophagy
#13
Tomonori Kimura, Jingyue Jia, Suresh Kumar, Seong Won Choi, Yuexi Gu, Michal Mudd, Nicolas Dupont, Shanya Jiang, Ryan Peters, Farzin Farzam, Ashish Jain, Keith A Lidke, Christopher M Adams, Terje Johansen, Vojo Deretic
Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL-1β is recognized by specialized secretory autophagy cargo receptor TRIM16 and that this receptor interacts with the R-SNARE Sec22b to recruit cargo to the LC3-II(+) sequestration membranes...
January 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27927092/an-rnai-screen-for-genes-involved-in-nanoscale-protrusion-formation-on-corneal-lens-in-drosophila-melanogaster
#14
Ryunosuke Minami, Chiaki Sato, Yumi Yamahama, Hideo Kubo, Takahiko Hariyama, Ken-Ichi Kimura
The "moth-eye" structure, which is observed on the surface of corneal lens in several insects, supports anti-reflective and self-cleaning functions due to nanoscale protrusions known as corneal nipples. Although the morphology and function of the "moth-eye" structure, are relatively well studied, the mechanism of protrusion formation from cell-secreted substances is unknown. In Drosophila melanogaster, a compound eye consists of approximately 800 facets, the surface of which is formed by the corneal lens with nanoscale protrusions...
December 2016: Zoological Science
https://www.readbyqxmd.com/read/27923985/the-get-system-inserts-the-tail-anchored-syp72-protein-into-endoplasmic-reticulum-membranes
#15
Renu Srivistava, Benjamin E Zalisko, Robert J Keenan, Stephen H Howell
The Arabidopsis genome encodes homologs of the Guided Entry of Tail anchored proteins (GET) system for the post-translational insertion of tail-anchored (TA) proteins into endoplasmic reticulum (ER) membranes. In yeast, TA proteins are loaded onto the cytosolic targeting factor Get3 and then delivered to the membrane-associated Get1/2 complex for insertion into ER membranes. The role of the GET system in Arabidopsis was investigated by monitoring the membrane insertion of a tail-anchored protein, SYP72, a syntaxin...
December 6, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27896523/a-cd57-ctl-degranulation-assay-effectively-identifies-familial-hemophagocytic-lymphohistiocytosis-type-3-patients
#16
Masayuki Hori, Takahiro Yasumi, Saeko Shimodera, Hirofumi Shibata, Eitaro Hiejima, Hirotsugu Oda, Kazushi Izawa, Tomoki Kawai, Masataka Ishimura, Naoko Nakano, Ryutaro Shirakawa, Ryuta Nishikomori, Hidetoshi Takada, Satoshi Morita, Hisanori Horiuchi, Osamu Ohara, Eiichi Ishii, Toshio Heike
PURPOSE: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic disorder that results in immune dysregulation. It requires prompt and accurate diagnosis. A natural killer (NK) cell degranulation assay is often used to screen for FHL3 patients. However, we recently encountered two cases of late-onset FHL3 carrying novel UNC13D missense mutations: in these cases, the degranulation assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded contradictory results...
November 28, 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27885029/the-atg-conjugation-systems-are-important-for-degradation-of-the-inner-autophagosomal-membrane
#17
Kotaro Tsuboyama, Ikuko Koyama-Honda, Yuriko Sakamaki, Masato Koike, Hideaki Morishita, Noboru Mizushima
In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with the lysosome to become the autolysosome. It has been thought that the autophagy-related (ATG) conjugation systems are required for autophagosome formation. Here, we found that autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17-positive autophagosome-like structures could be generated even in the absence of the ATG conjugation systems, although at a reduced rate...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27851964/caps1-rna-editing-promotes-dense-core-vesicle-exocytosis
#18
Kotaro Miyake, Toshio Ohta, Hisako Nakayama, Nobutaka Doe, Yuri Terao, Eiji Oiki, Izumi Nagatomo, Yui Yamashita, Takaya Abe, Kazuko Nishikura, Atsushi Kumanogoh, Kouichi Hashimoto, Yukio Kawahara
Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 pre-mRNA is known to undergo adenosine-to-inosine RNA editing in its coding region, which results in a glutamate-to-glycine conversion at a site in its C-terminal region. However, the physiological significance of CAPS1 RNA editing remains elusive. Here, we created mutant mice in which edited CAPS1 was solely expressed. These mice were lean due to increased energy expenditure caused by physical hyperactivity...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27836773/distinct-roles-of-prolactin-epidermal-growth-factor-and-glucocorticoids-in-%C3%AE-casein-secretion-pathway-in-lactating-mammary-epithelial-cells
#19
Ken Kobayashi, Shoko Oyama, Chinatsu Kuki, Yusaku Tsugami, Kota Matsunaga, Takahiro Suzuki, Takanori Nishimura
Beta-casein is a secretory protein contained in milk. Mammary epithelial cells (MECs) synthesize and secrete β-casein during lactation. However, it remains unclear how the β-casein secretion pathway is developed after parturition. In this study, we focused on prolactin (PRL), epidermal growth factor (EGF), and glucocorticoids, which increase in blood plasma and milk around parturition. MECs cultured with PRL, EGF and dexamethasone (DEX: glucocorticoid analog) developed the β-casein secretion pathway. In the absence of PRL, MECs hardly expressed β-casein...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27832597/caveolin-1-regulation-of-disrupted-in-schizophrenia-1-as-a-potential-therapeutic-target-for-schizophrenia
#20
Adam Kassan, Junji Egawa, Zheng Zhang, Angels Almenar-Queralt, Quynh My Nguyen, Yasaman Lajevardi, Kaitlyn Kim, Edmund Posadas, Dilip V Jeste, David M Roth, Piyush M Patel, Hemal H Patel, Brian P Head
BACKGROUND: Schizophrenia is a debilitating psychiatric disorder manifested in early adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptible gene for schizophrenia (54, 76, 101) implicated in neuronal development, brain maturation and neuroplasticity (12, 20). Therefore, DISC1 is a promising candidate gene for schizophrenia, but the molecular mechanisms underlying its role in the pathogenesis of the disease are still poorly understood. Interestingly, Caveolin-1 (Cav-1), a cholesterol binding and scaffolding protein, regulates neuronal signal transduction and promotes neuroplasticity...
November 2, 2016: Journal of Neurophysiology
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