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https://www.readbyqxmd.com/read/27877110/forward-genetic-screen-in-caenorhabditis-elegans-suggests-f57a10-2-and-acp-4-as-suppressors-of-c9orf72-related-phenotypes
#1
Xin Wang, Limin Hao, Taixiang Saur, Katelyn Joyal, Ying Zhao, Desheng Zhai, Jie Li, Mochtar Pribadi, Giovanni Coppola, Bruce M Cohen, Edgar A Buttner
An abnormally expanded GGGGCC repeat in C9ORF72 is the most frequent causal mutation associated with amyotrophic lateral sclerosis (ALS)/frontotemporal lobar degeneration (FTLD). Both gain-of-function (gf) and loss-of-function (lf) mechanisms have been involved in C9ORF72 related ALS/FTLD. The gf mechanism of C9ORF72 has been studied in various animal models but not in C. elegans. In the present study, we described mutant C9ORF72 modeling in C. elegans and report the finding of two suppressor genes. We made transgenes containing 9 or 29 repeats of GGGGCC in C9ORF72, driven by either the hsp-16 promoters or the unc-119 promoter...
2016: Frontiers in Molecular Neuroscience
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
#2
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...
November 9, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27810382/immunohistochemical-localization-of-snare-core-proteins-in-intrapulpal-and-intradentinal-nerve-fibers-of-rat-molar-teeth
#3
Shiho Honma, Kohki Kadono, Akiyo Kawano, Satoshi Wakisaka
OBJECTIVE: The present study was designed to elucidate whether three soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) core proteins, syntaxin-1, synaptosomal-associated protein of 25kDa (SNAP-25), and vesicle-associated membrane protein-2 (VAMP-2), are present in the dental pulp of the rat molar at both the light and electron microscopic levels. DESIGN: Immunohistochemistry for protein gene product 9.5 (PGP 9.5), a pan-neuronal marker, syntaxin-1, SNAP-25, and VAMP-2 was performed on decalcified rat molars for light and electron microscopic analyses...
October 26, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27694038/targeting-mast-cells-uncovering-prolific-therapeutic-role-in-myriad-diseases
#4
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors...
September 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27625359/respective-contributions-of-single-and-compound-granule-fusion-to-secretion-by-activated-platelets
#5
Anita Eckly, Jean-Yves Rinckel, Fabienne Proamer, Neslihan Ulas, Smita Joshi, Sidney W Whiteheart, Christian Gachet
While granule secretion is pivotal in many platelet responses, the fusion routes of α and δ granule release remain uncertain. We used a 3D reconstruction approach, based on electron microscopy, to visualize the spatial organization of granules in unstimulated and activated platelets. Two modes of exocytosis, single and compound exocytosis, were identified: a single mode which leads to release of the contents of individual granules and a compound mode which leads to the formation of granule-to-granule fusion, resulting in the formation of large multi-granular compartments...
September 13, 2016: Blood
https://www.readbyqxmd.com/read/27616736/vamp2-is-implicated-in-the-secretion-of-antibodies-by-human-plasma-cells-and-can-be-replaced-by-other-synaptobrevins
#6
Laura Gómez-Jaramillo, Raquel Romero-García, Gema Jiménez-Gómez, Lisa Riegle, Ana Belén Ramos-Amaya, José Antonio Brieva, Marie Kelly-Worden, Antonio Campos-Caro
The production and secretion of antibodies by human plasma cells (PCs) are two essential processes of humoral immunity. The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which are located in the plasma membrane (t-SNAREs) and in the antibody-carrying vesicle membrane (v-SNARE), and mediate the fusion of both membranes. We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion. Here, using human PCs and antibody-secreting cell lines, we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein (VAMP) isoforms, demonstrating that all isoforms (with the exception of VAMP1) are expressed by the referenced cells...
September 12, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27571895/neuronal-overexpression-of-human-vapb-slows-motor-impairment-and-neuromuscular-denervation-in-a-mouse-model-of-als
#7
Ji-Yoen Kim, Ava Jang, Rohit Reddy, Wan Hee Yoon, Joanna L Jankowsky
Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB mutations cause motor neuron disease is unclear, but studies of the most common P56S variant suggest both loss of function and dominant-negative sequestration of wild-type protein. Diminished levels of VAPB and its proteolytic cleavage fragment have also been reported in sporadic ALS cases, suggesting that VAPB loss of function may be a common mechanism of disease...
August 29, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27527271/neurotoxins-from-clostridium-botulinum-serotype-a-isolated-from-the-soil-of-mendoza-argentina-differ-from-the-a-hall-archetype-and-from-that-causing-infant-botulism
#8
P Caballero, M Troncoso, S I Patterson, C López Gómez, R Fernandez, M A Sosa
The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain...
October 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27515081/imaging-synaptic-vesicle-exocytosis-endocytosis-with-ph-sensitive-fluorescent-proteins
#9
Olusoji A T Afuwape, Ege T Kavalali
The introduction of pHluorin, a pH-sensitive GFP, by Miesenbock and colleagues provided a versatile tool to studies of vesicle trafficking, in particular synaptic vesicle exocytosis and endocytosis. By tagging pHluorin to the luminal region of the synaptic vesicular protein synaptobrevin (also called VAMP, vesicle-associated membrane protein) or other synaptic vesicle-specific proteins such as the vesicular glutamate transporter-1, we are able to directly track synaptic vesicle endocytosis in response to stimuli in a molecularly specific manner...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27499056/treatment-with-the-selective-serotonin-reuptake-inhibitor-fluoxetine-attenuates-the-fish-hypoxia-response
#10
Jennifer M Panlilio, Sara Marin, Marissa B Lobl, M Danielle McDonald
The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27446609/combinations-of-sirnas-against-la-autoantigen-with-ns5b-or-hvap-a-have-additive-effect-on-inhibition-of-hcv-replication
#11
Anirban Mandal, Krishna Kumar Ganta, Binay Chaubey
Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle...
2016: Hepatitis Research and Treatment
https://www.readbyqxmd.com/read/27443638/the-first-non-clostridial-botulinum-like-toxin-cleaves-vamp-within-the-juxtamembrane-domain
#12
Irene Zornetta, Domenico Azarnia Tehran, Giorgio Arrigoni, Fabrizio Anniballi, Luca Bano, Oneda Leka, Giuseppe Zanotti, Thomas Binz, Cesare Montecucco
The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27402227/phosphorylation-of-residues-inside-the-snare-complex-suppresses-secretory-vesicle-fusion
#13
Seth Malmersjö, Serena Di Palma, Jiajie Diao, Ying Lai, Richard A Pfuetzner, Austin L Wang, Moira A McMahon, Arnold Hayer, Matthew Porteus, Bernd Bodenmiller, Axel T Brunger, Tobias Meyer
Membrane fusion is essential for eukaryotic life, requiring SNARE proteins to zipper up in an α-helical bundle to pull two membranes together. Here, we show that vesicle fusion can be suppressed by phosphorylation of core conserved residues inside the SNARE domain. We took a proteomics approach using a PKCB knockout mast cell model and found that the key mast cell secretory protein VAMP8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP8 phosphorylation reduces vesicle fusion in vitro and suppresses secretion in living cells, allowing vesicles to dock but preventing fusion with the plasma membrane...
August 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27401904/does-a-learned-journal-require-regular-re-vamping
#14
EDITORIAL
A van Belkum
No abstract text is available yet for this article.
August 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27274421/accuracy-of-self-reported-foot-strike-pattern-in-intercollegiate-and-recreational-runners-during-shod-running
#15
Michael B Bade, Katie Aaron, Thomas G McPoil
BACKGROUND: Clinicians are interested in the foot strike pattern (FSP) in runners because of the suggested relationship between the strike pattern and lower extremity injury. PURPOSE: The purpose of this study was to assess the ability of collegiate cross-country runners and recreational runners to self-report their foot strike pattern during running. STUDY DESIGN: Cross-sectional Study. METHODS: Twenty-three collegiate cross-country and 23 recreational runners voluntarily consented to participate...
June 2016: International Journal of Sports Physical Therapy
https://www.readbyqxmd.com/read/27183589/protein-tyrosine-kinase-fyn-regulates-tlr4-elicited-responses-on-mast-cells-controlling-the-function-of-a-pp2a-pkc%C3%AE-%C3%AE-signaling-node-leading-to-tnf-secretion
#16
Alejandro Martín-Ávila, Jaciel Medina-Tamayo, Alfredo Ibarra-Sánchez, Genaro Vázquez-Victorio, Jorge Iván Castillo-Arellano, Alma Cristal Hernández-Mondragón, Juan Rivera, Iris K Madera-Salcedo, Ulrich Blank, Marina Macías-Silva, Claudia González-Espinosa
Mast cells produce proinflammatory cytokines in response to TLR4 ligands, but the signaling pathways involved are not fully described. In this study, the participation of the Src family kinase Fyn in the production of TNF after stimulation with LPS was evaluated using bone marrow-derived mast cells from wild-type and Fyn-deficient mice. Fyn(-/-) cells showed higher LPS-induced secretion of preformed and de novo-synthesized TNF. In both cell types, TNF colocalized with vesicle-associated membrane protein (VAMP)3-positive compartments...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27125645/manganese-exposure-disrupts-snare-protein-complex-mediated-vesicle-fusion-in-primary-cultured-neurons
#17
Can Wang, Bin Xu, Qi-Fan Song, Yu Deng, Wei Liu, Zhao-Fa Xu
Overexposure to manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether the protein expression and their interaction of SNARE complex associated proteins were the media between Mn exposure and neurotransmitter vesicle fusion disorders. After the neurons were respectively exposed to Mn (0-200 μM) for 0, 6, 12, 18, 24 h, there were different degrees of cell injury in neurons...
April 29, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27109323/the-role-of-tlr2-in-the-acute-inflammatory-response-induced-by-bothrops-atrox-snake-venom
#18
Vanessa Moreira, Catarina Teixeira, Henrique Borges da Silva, Maria Regina D'Império Lima, Maria Cristina Dos-Santos
Envenomation by snakes of the species Bothrops atrox induces local and systemic effects. Local effects include drastic tissue damage and a marked inflammatory response as a result of the synthesis and release of a variety of protein and lipid mediators. Toll-like receptor (TLR) signaling pathways can play an important role in this response, leading to synthesis of these inflammatory mediators. This study investigated the influence of TLR2 on the acute inflammatory response induced by Bothrops atrox venom. Wild-type C57BL/6 mice (WT) and TLR2 gene knockout mice (TLR2(-/-)) were injected with Bothrops atrox venom (BaV), and the following responses to the venom were assessed in peritoneal exudate: leukocyte accumulation; release of mediators, including CCL-2, IL-10, IL-1β, IL-6 and LTB4; protein expression of COX-1 and COX-2; and quantification of their products PGE2 and TXA2...
August 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27068960/touch%C3%A3-stard3-and-stard3nl-tether-the-er-to-endosomes
#19
REVIEW
Léa P Wilhelm, Catherine Tomasetto, Fabien Alpy
Membrane contact sites (MCSs) are subcellular regions where the membranes of distinct organelles come into close apposition. These specialized areas of the cell, which are involved in inter-organelle metabolite exchange, are scaffolded by specific complexes. STARD3 [StAR (steroidogenic acute regulatory protein)-related lipid transfer domain-3] and its close paralogue STARD3NL (STARD3 N-terminal like) are involved in the formation of contacts between late-endosomes and the endoplasmic reticulum (ER). The lipid transfer protein (LTP) STARD3 and STARD3NL, which are both anchored on the limiting membrane of late endosomes (LEs), interact with ER-anchored VAP [VAMP (vesicle-associated membrane protein)-associated protein] (VAP-A and VAP-B) proteins...
April 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27054443/ldl-cholesterol-transport-to-the-endoplasmic-reticulum-current-concepts
#20
Simon G Pfisterer, Johan Peränen, Elina Ikonen
PURPOSE OF REVIEW: In this article, we summarize the present information related to the export of LDL-derived cholesterol from late endosomes, with a focus on Nieman-Pick disease, type C1 (NPC1) cholesterol delivery toward the endoplasmic reticulum (ER). We review data suggesting that several pathways may operate in parallel, including membrane transport routes and membrane contact sites (MCSs). RECENT FINDINGS: There is increasing appreciation that MCSs provide an important mechanism for intermembrane lipid transfer...
June 2016: Current Opinion in Lipidology
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