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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
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
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
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
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
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
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
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
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
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
A van Belkum
No abstract text is available yet for this article.
August 2016: European Journal of Clinical Microbiology & Infectious Diseases
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
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
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
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
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
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
J-G Shin, D-Y Kim, J-M Seo, J-T Oh, K-W Park, H-Y Kim, B L Park, J-H Kim, H D Shin
BACKGROUND: Hirschsprung disease (HSCR) is a congenital bowel disease caused by the absence of nerve cells in portions of the intestine. Our recent genome-wide association study has identified a variant (rs1254900) of vesicle-associated membrane protein 5 (VAMP5) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. In addition, VAMP5 is a member of the VAMP/synaptobrevin protein complex, which participates in nerve signal transduction by regulating the vesicular fusion of the neurotransmitter in synaptic transmission...
July 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Sarah E Murphy, Tim P Levine
Dysfunction of VAMP-associated protein (VAP) is associated with neurodegeneration, both Amyotrophic Lateral Sclerosis and Parkinson's disease. Here we summarize what is known about the intracellular interactions of VAP in humans and model organisms. VAP is a simple, small and highly conserved protein on the cytoplasmic face of the endoplasmic reticulum (ER). It is the sole protein on that large organelle that acts as a receptor for cytoplasmic proteins. This may explain the extremely wide range of interacting partners of VAP, with components of many cellular pathways binding it to access the ER...
August 2016: Biochimica et Biophysica Acta
Yeun Ju Kim, Maria Luisa Guzman-Hernandez, Eva Wisniewski, Nicolas Echeverria, Tamas Balla
Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases. Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function...
February 2016: Biochemical Society Transactions
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