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https://www.readbyqxmd.com/read/28103630/orientia-tsutsugamushi-ank9-is-a-multifunctional-effector-that-utilizes-a-novel-grip-like-golgi-localization-domain-for-golgi-to-endoplasmic-reticulum-trafficking-and-interacts-with-host-copb2
#1
Andrea R Beyer, Kyle G Rodino, Lauren VieBrock, Ryan S Green, Brittney K Tegels, Lee D Oliver, Richard T Marconi, Jason A Carlyon
Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that afflicts one million people annually. This obligate intracellular bacterium boasts one of the largest microbial arsenals of ankyrin repeat-containing protein (Ank) effectors, most of which target the endoplasmic reticulum (ER) by undefined mechanisms. Ank9 is the only one proven to function during infection. Here, we demonstrate that Ank9 bears a motif that mimics the GRIP domain of eukaryotic golgins and is necessary and sufficient for its Golgi localization...
January 19, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28103313/mycobacterium-marinum-degrades-both-triacylglycerols-and-phospholipids-from-its-dictyostelium-host-to-synthesise-its-own-triacylglycerols-and-generate-lipid-inclusions
#2
Caroline Barisch, Thierry Soldati
During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102850/japanese-encephalitis-virus-induces-human-neural-stem-progenitor-cell-death-by-elevating-grp78-phb-and-hnrnpc-through-er-stress
#3
Sriparna Mukherjee, Noopur Singh, Nabonita Sengupta, Mahar Fatima, Pankaj Seth, Anita Mahadevan, Susarla Krishna Shankar, Arindam Bhattacharyya, Anirban Basu
Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102736/dengue-and-zika-viruses-subvert-reticulophagy-by-ns2b3-mediated-cleavage-of-fam134b
#4
Nicholas J Lennemann, Carolyn B Coyne
The endoplasmic reticulum (ER) is exploited by a number of diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. In order to maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autophagy that leads to ER degradation...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102470/neuronal-ryanodine-receptors-in-development-and-aging
#5
REVIEW
Nawaf Abu-Omar, Jogita Das, Vivian Szeto, Zhong-Ping Feng
Ryanodine receptors (RyRs) are intracellular calcium-release channels found on the endoplasmic reticulum of all cells. All three RyR isoforms, RyR1-3, are expressed in the brain, with RyR2 predominating. RyRs are localized within the soma, axons, dendritic spines, and presynaptic terminals of neurons. RyRs are highly expressed in the cerebellum, hippocampus, olfactory region, basal ganglia, and cerebral cortex. During the physiological processes of development and aging, the intracellular calcium homeostasis is largely regulated by RyRs...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28102311/plin2-is-a-key-regulator-of-the-unfolded-protein-response-and-endoplasmic-reticulum-stress-resolution-in-pancreatic-%C3%AE-cells
#6
Elaine Chen, Tsung Huang Tsai, Lan Li, Pradip Saha, Lawrence Chan, Benny Hung-Junn Chang
Progressive pancreatic β cell failure underlies the transition of impaired glucose tolerance to overt diabetes; endoplasmic reticulum (ER) stress expedites β cell failure in this situation. ER stress can be elicited by lipotoxicity and an increased demand for insulin in diabetes. We previously reported that the lipid droplet protein perilipin 2 (PLIN2) modulates lipid homeostasis in the liver. Here, we show that PLIN2 modulates the unfolded protein response (UPR) and ER stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102201/direct-pip2-binding-mediates-stable-oligomer-formation-of-the-serotonin-transporter
#7
Andreas Anderluh, Tina Hofmaier, Enrico Klotzsch, Oliver Kudlacek, Thomas Stockner, Harald H Sitte, Gerhard J Schütz
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101220/antitumor-effect-of-forbesione-isolated-from-garcinia-hanburyi-on-cholangiocarcinoma-in-vitro-and-in-vivo
#8
Parichart Boueroy, Chariya Hahnvajanawong, Thidarut Boonmars, Sunitta Saensa-Ard, Natthinee Anantachoke, Kulthida Vaeteewoottacharn, Vichai Reutrakul
Cholangiocarcinoma (CCA) is a malignancy with no effective therapy and poor prognosis. Forbesione, a caged xanthone isolated from Garcinia hanburyi, has been reported to inhibit proliferation and to induce apoptosis in human CCA cell lines. The present study aimed to further explore the potential anticancer properties of forbesione by testing its effects against the hamster CCA cell line Ham-1 in vitro and in vivo. It was observed that forbesione inhibited the growth of Ham-1 cells in vitro and suppressed Ham-1 growth as allograft in hamsters by inducing cell cycle arrest at the S phase...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100868/growth-inhibition-of-refractory-human-gallbladder-cancer-cells-by-retinol-and-its-mechanism-of-action
#9
Chuan Li, Masahiko Imai, Shinya Hasegawa, Masahiro Yamasaki, Noriko Takahashi
Among the constituents of the essential nutrient vitamin A, retinol is a potent suppressor of refractory cancer cell growth linked to tumor progression, showing greater efficacy than retinoic acid (RA). However, the mechanisms of retinol action on human refractory cancer are not known well. In the current study, we examined the actions of retinol on proliferation of human gallbladder cancer NOZ C-1 cells. Retinol and RA inhibited the proliferation of human NOZ C-1 cells in dose-dependent manner, while RA was less potent than retinol...
January 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28100841/cannabinoids-a-new-weapon-against-cancer
#10
Małgorzata Pokrywka, Joanna Góralska, Bogdan Solnica
Cannabis has been cultivated by man since Neolithic times. It was used, among others for fiber and rope production, recreational purposes and as an excellent therapeutic agent. The isolation and characterization of the structure of one of the main active ingredients of cannabis - Δ9 - tetrahydrocannabinol as well the discovery of its cannabinoid binding receptors CB1 and CB2, has been a milestone in the study of the possibilities of the uses of Cannabis sativa and related products in modern medicine. Many scientific studies indicate the potential use of cannabinoids in the fight against cancer...
December 29, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100648/multi-scale-structural-analysis-of-plant-er-pm-contact-sites
#11
Heather E McFarlane, Eun Kyoung Lee, Laura S van Bezouwen, Bradford Ross, Abel Rosado, A Lacey Samuels
Membrane contact sites (MCS) are recognized across eukaryotic systems as important nanostructures. Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) are involved in excitation-contraction coupling, signalling, and plant responses to stress. In this report, we perform a multi-scale structural analysis of Arabidopsis EPCS that combine live cell imaging, quantitative transmission electron microscopy (TEM), and electron tomography over a developmental gradient. To place EPCS in the context of the entire cortical ER, we examined GFP-HDEL in living cells over a developmental gradient, then SYT1-GFP was used as a specific marker of EPCS...
January 18, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28100484/atf6-knock-down-decreases-apoptosis-arrests-the-s-phase-of-the-cell-cycle-and-increases-steroid-hormone-production-in-mouse-granulosa-cells
#12
Yongjie Xiong, Huatao Chen, Pengfei Lin, Aihua Wang, Lei Wang, Yaping Jin
Activating transcription factor 6 (ATF6) is an important factor in the endoplasmic reticulum (ER) stress signaling pathway. The aim of this study was to assess the role of ATF6 in mouse granulosa cells with respect to apoptosis, the cell cycle, and steroid hormone production, as well as several key genes related to follicular development, via RNA interference, immunohistochemical staining, real-time quantitative polymerase chain reaction, western blotting, flow cytometry, TUNEL assay, and ELISA. Immunohistochemical staining revealed that ATF6 was extensively distributed in the granulosa cells of various ovarian follicles and oocytes in adult female mice...
January 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28099849/cyclic-amp-recruits-a-discrete-intracellular-ca-2-store-by-unmasking-hypersensitive-ip3-receptors
#13
Vera Konieczny, Stephen C Tovey, Stefania Mataragka, David L Prole, Colin W Taylor
Inositol 1,4,5-trisphosphate (IP3) stimulates Ca(2+) release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP3 and cAMP, respectively. PTH alone had no effect on the cytosolic Ca(2+) concentration, but it potentiated the Ca(2+) signals evoked by carbachol. Surprisingly, however, the intracellular Ca(2+) stores that respond to carbachol alone could be both emptied and refilled without affecting the subsequent response to PTH...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099257/antifibrotic-effect-of-saturated-fatty-acids-via-endoplasmic-reticulum-stress-response-in-rat-pancreatic-stellate-cells
#14
Lingaku Lee, Tetsuhide Ito, Taichi Nakamura, Robert T Jensen, Hisato Igarashi, Ryoichi Takayanagi
OBJECTIVES: We investigated the effect of saturated fatty acids on chronic pancreatitis pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis. METHODS: Wistar Bonn/Kobori rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin, an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability, and apoptosis were examined...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28098884/renin-angiotensin-system-activation-accelerates-atherosclerosis-in-experimental-renal-failure-by-promoting-endoplasmic-reticulum-stress-related-inflammation
#15
Jia Yang, Xi Zhang, Xinyi Yu, Weixue Tang, Hua Gan
In this study, we investigated the association between the renin-angiotensin system (RAS), endoplasmic reticulum (ER) stress and atherosclerosis (AS) in uremic apolipoprotein E knockout (apoE-/-) mice. Mild uremia was induced by a 5/6 nephrectomy (5/6 Nx) in 10-week-old apoE-/- mice. Four weeks after nephrectomy, the mice received losartan or no treatment for 16 weeks. Sham-operated mice served as the controls. We found that uremia accelerated AS at the aortic root. The activation of ER stress and the significant upregulation of pro-inflammatory cytokines and chemokines were observed in the uremic mice...
January 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28098843/perm-hypothesis-the-fundamental-machinery-able-to-elucidate-the-role-of-xenobiotics-and-hormesis-in-cell-survival-and-homeostasis
#16
REVIEW
Salvatore Chirumbolo, Geir Bjørklund
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response...
January 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098200/cullin-7-mediates-proteasomal-and-lysosomal-degradations-of-rat-eag1-potassium-channels
#17
Po-Hao Hsu, Yu-Ting Ma, Ya-Ching Fang, Jing-Jia Huang, Yu-Ling Gan, Pei-Tzu Chang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Mammalian Eag1 (Kv10.1) potassium (K(+)) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K(+) channel have been associated with congenital neurodevelopmental anomalies. Currently very little is known about the molecules mediating protein synthesis and degradation of Eag1 channels. Herein we aim to ascertain the protein degradation mechanism of rat Eag1 (rEag1). We identified cullin 7 (Cul7), a member of the cullin-based E3 ubiquitin ligase family, as a novel rEag1 binding partner...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#18
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28096492/identification-of-glutaminyl-cyclase-genes-involved-in-pyroglutamate-modification-of-fungal-lignocellulolytic-enzymes
#19
Vincent W Wu, Craig M Dana, Anthony T Iavarone, Douglas S Clark, N Louise Glass
: The breakdown of plant biomass to simple sugars is essential for the production of second-generation biofuels and high-value bioproducts. Currently, enzymes produced from filamentous fungi are used for deconstructing plant cell wall polysaccharides into fermentable sugars for biorefinery applications. A post-translational N-terminal pyroglutamate modification observed in some of these enzymes occurs when N-terminal glutamine or glutamate is cyclized to form a five-membered ring. This modification has been shown to confer resistance to thermal denaturation for CBH-1 and EG-1 cellulases...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096411/hepatitis-e-virus-orf3-is-a-functional-ion-channel-required-for-release-of-infectious-particles
#20
Qiang Ding, Brigitte Heller, Juan M V Capuccino, Bokai Song, Ila Nimgaonkar, Gabriela Hrebikova, Jorge E Contreras, Alexander Ploss
Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally. Of HEV's three ORFs, the function of ORF3 has remained elusive. Here, we demonstrate that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endoplasmic reticulum (ER)-derived membranes. HEV ORF3 shares several structural features with class I viroporins, and the function of HEV ORF3 can be maintained by replacing it with the well-characterized viroporin influenza A virus (IAV) matrix-2 protein...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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