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https://www.readbyqxmd.com/read/29916038/copii-dependent-er-export-in-animal-cells-adaptation-and-control-for-diverse-cargo
#1
REVIEW
Janine McCaughey, David J Stephens
The export of newly synthesized proteins from the endoplasmic reticulum is fundamental to the ongoing maintenance of cell and tissue structure and function. After co-translational translocation into the ER, proteins destined for downstream intracellular compartments or secretion from the cell are sorted and packaged into transport vesicles by the COPII coat protein complex. The fundamental discovery and characterization of the pathway has now been augmented by a greater understanding of the role of COPII in diverse aspects of cell function...
June 18, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29913427/formononetin-inhibits-neuroinflammation-and-increases-estrogen-receptor-beta-er%C3%AE-protein-expression-in-bv2-microglia
#2
Abdelmeniem El-Bakoush, Olumayokun A Olajide
Formononetin is a bioactive non-steroidal polyphenol found in a variety of plants. In this study we evaluated the effects of formononetin on neuroinflammation in LPS-stimulated BV2 microglia. Results showed that formononetin significantly reduced the production of TNF-α, IL-6 and IL-1β, nitrite and PGE2 , as well as protein levels of iNOS and COX-2. Reporter gene assays showed that formononetin produced inhibition of NF-κB luciferase activity in HEK293 cells stimulated with TNF-α. Immunoblotting experiments revealed an inhibition of IKKα phosphorylation, with the resultant attenuation of phosphorylation and degradation of IκBα following LPS stimulation...
June 15, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29906559/peroxiredoxin-5-prevents-iron-overload-induced-neuronal-death-by-inhibiting-mitochondrial-fragmentation-and-endoplasmic-reticulum-stress-in-mouse-hippocampal-ht-22-cells
#3
Dong Gil Lee, Min Kyoung Kam, Kyung Min Kim, Han Seop Kim, Oh-Shin Kwon, Hyun-Shik Lee, Dong-Seok Lee
Iron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca2+ , endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood. In this study, we demonstrated that iron overload induces ROS production earlier in the ER than in the mitochondria, and peroxiredoxin 5 (Prx5), which is a kind of antioxidant induced by iron overload, prevents iron overload-induced mitochondrial fragmentation mediated by contact with ER and translocation of Drp1, by inhibiting ROS production and calcium/calcineurin pathway in HT-22 mouse hippocampal neuronal cells...
June 12, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29890130/the-basic-route-of-the-nuclear-translocation-porcine-growth-hormone-gh-growth-hormone-receptor-ghr-complex-pgh-ghr-in-porcine-hepatocytes
#4
Lan Hainan, Liu Huilin, Mahamad Khan, Zheng Xin, Yang YuJiang, Zhang Hui, Yao Naiquan
Traditional views suggest that growth hormone and the growth hormone receptor (GH/GHR complex) exert their functions only on the plasma membrane. This paradigm, however, has been challenged by recent new findings that the GH/GHR complex could translocate into cell nuclei where they could still exhibit important physiological functions. We also reported the nuclear localization of porcine GH/GHR and their potential functions in porcine hepatocytes. However, the basic path of pGH/GHR's nuclear translocation remains unclear...
June 8, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29872748/analysis-of-tail-anchored-protein-translocation-pathway-in-plants
#5
M S Manu, Deepanjan Ghosh, Bhushan P Chaudhari, Sureshkumar Ramasamy
Tail-anchored (TA) proteins are a special class of membrane proteins that carry out vital functions in all living cells. Targeting mechanisms of TA proteins are investigated as the best example for post-translational protein targeting in yeast. Of the several mechanisms, Guided Entry of Tail-anchored protein (GET) pathway plays a major role in TA protein targeting. Many in silico and in vivo analyses are geared to identify TA proteins and their targeting mechanisms in different systems including Arabidopsis thaliana ...
July 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29870684/the-binding-of-tbk1-to-sting-requires-exocytic-membrane-traffic-from-the-er
#6
Emari Ogawa, Kojiro Mukai, Kota Saito, Hiroyuki Arai, Tomohiko Taguchi
Stimulator of interferon genes (STING) is essential for the type I interferon and pro-inflammatory responses against DNA pathogens. In response to the presence of cytosolic DNA, STING translocates from the endoplasmic reticulum (ER) to the Golgi, and activates TANK-binding kinase 1 (TBK1), a cytosolic kinase that is essential for the activation of STING-dependent downstream signalling. The organelles where TBK1 binds to STING remain unknown. Here we show that TBK1 binds to STING at the Golgi, not at the ER...
June 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29788888/scap-srebps-are-central-players-in-lipid-metabolism-and-novel-metabolic-targets-in-cancer-therapy
#7
Xiang Cheng, Jianying Li, Deliang Guo
Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29783744/interplay-between-er-ca-2-binding-proteins-stim1-and-stim2-is-required-for-store-operated-ca-2-entry
#8
Heather A Nelson, Colin A Leech, Richard F Kopp, Michael W Roe
Store-operated calcium entry (SOCE), a fundamentally important homeostatic and Ca2+ signaling pathway in many types of cells, is activated by the direct interaction of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum (ER) Ca2+ -binding protein, with Ca2+ -selective Orai1 channels localized in the plasma membrane. While much is known about the regulation of SOCE by STIM1, the role of stromal interaction molecule 2 (STIM2) in SOCE remains incompletely understood. Here, using clustered regularly interspaced short palindromic repeats -CRISPR associated protein 9 (CRISPR-Cas9) genomic editing and molecular imaging, we investigated the function of STIM2 in NIH 3T3 fibroblast and αT3 cell SOCE...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783743/cell-propagation-of-cholera-toxin-cta-adp-ribosylating-factor-by-exosome-mediated-transfer
#9
Cristiana Zanetti, Angelo Gallina, Alessia Fabbri, Sofia Parisi, Angela Palermo, Katia Fecchi, Zaira Boussadia, Maria Carollo, Mario Falchi, Luca Pasquini, Maria Luisa Fiani, Massimo Sargiacomo
In this study, we report how the cholera toxin (CT) A subunit (CTA), the enzyme moiety responsible for signaling alteration in host cells, enters the exosomal pathway, secretes extracellularly, transmits itself to a cell population. The first evidence for long-term transmission of CT's toxic effect via extracellular vesicles was obtained in Chinese hamster ovary (CHO) cells. To follow the CT intracellular route towards exosome secretion, we used a novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29781562/il-6-triggers-the-migration-and-invasion-of-oestrogen-receptor-negative-breast-cancer-cells-via-regulation-of-hippo-pathways
#10
Lingmi Hou, Shaoli Xie, Guanwu Li, Bin Xiong, Yanchun Gao, Xiaobo Zhao, Jiani Hu, Shishan Deng, Jun Jiang
Breast cancer is one of the major challenges for women's health. However, the role and mechanisms of interleukins (ILs) on the progression of breast cancer are not well illustrated. Our present study revealed that the expression of IL-6 and IL-8 was significantly increased in oestrogen receptor negative (ER-) breast cancer cells. Increased expression of IL-6 was observed in 83.9% (26/31) ER- breast cancer tissues as compared with their matched adjacent normal tissues. In vitro studies indicated that IL-6 can significantly promote the migration and invasion of ER- breast cancer cells via increasing the dephosphorylation, nuclear translocation and transcriptional activities of YAP in breast cancer cells...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29775898/particle-induced-sirt1-downregulation-promotes-osteoclastogenesis-and-osteolysis-through-er-stress-regulation
#11
Liang Zhang, Dongmei Bao, Peng Li, Zhidong Lu, Long Pang, Zhirong Chen, Haohui Guo, Zhihui Gao, Qunhua Jin
BACKGROUND: Sirtuin 1 (SIRT1) downregulation has been found to be induced by wear particles in aseptic prosthesis loosening (APL). Osteoclastogenesis and osteoclast activation are the main pathological factors associated with APL. However, whether SIRT1 downregulation contributes to the formation and activation of osteoclasts through the induction of endoplasmic reticulum (ER) stress is unclear. METHODS: To address this, an osteolysis mouse model was used in which animals were treated with the SIRT1 activator, resveratrol (RES), or an ER stress inhibitor, 4-PBA, for two weeks...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29765047/tip60-mediated-lipin-1-acetylation-and-er-translocation-determine-triacylglycerol-synthesis-rate
#12
Terytty Yang Li, Lintao Song, Yu Sun, Jingyi Li, Cong Yi, Sin Man Lam, Dijin Xu, Linkang Zhou, Xiaotong Li, Ying Yang, Chen-Song Zhang, Changchuan Xie, Xi Huang, Guanghou Shui, Shu-Yong Lin, Karen Reue, Sheng-Cai Lin
Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser86 phosphorylation site of acetyltransferase Tip60 (Tip60 SA/SA ) display remarkably reduced body fat mass, and Tip60 SA/SA females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764906/eb1-traps-stim1-and-regulates-local-store-operated-ca-2-entry
#13
Qiao-Chu Wang, Xi Wang, Tie-Shan Tang
STIM1 activates store-operated Ca2+ entry when Ca2+ in the endoplasmic reticulum (ER) is depleted. In this issue, Chang et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201711151) demonstrate that EB1 traps STIM1 at dynamic contacts between the ER and microtubule plus ends, delaying STIM1 translocation to ER-plasma membrane junctions and preventing Ca2+ overload.
May 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29761100/moving-the-cellular-peptidome-by-transporters
#14
REVIEW
Rupert Abele, Robert Tampé
Living matter is defined by metastability, implying a tightly balanced synthesis and turnover of cellular components. The first step of eukaryotic protein degradation via the ubiquitin-proteasome system (UPS) leads to peptides, which are subsequently degraded to single amino acids by an armada of proteases. A small fraction of peptides, however, escapes further cytosolic destruction and is transported by ATP-binding cassette (ABC) transporters into the endoplasmic reticulum (ER) and lysosomes. The ER-resident heterodimeric transporter associated with antigen processing (TAP) is a crucial component in adaptive immunity for the transport and loading of peptides onto major histocompatibility complex class I (MHC I) molecules...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29760094/salicylic-acid-independent-role-of-npr1-is-required-for-protection-from-proteotoxic-stress-in-the-plant-endoplasmic-reticulum
#15
Ya-Shiuan Lai, Luciana Renna, John Yarema, Cristina Ruberti, Sheng Yang He, Federica Brandizzi
The unfolded protein response (UPR) is an ancient signaling pathway designed to protect cells from the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER). Because misregulation of the UPR is potentially lethal, a stringent surveillance signaling system must be in place to modulate the UPR. The major signaling arms of the plant UPR have been discovered and rely on the transcriptional activity of the transcription factors bZIP60 and bZIP28 and on the kinase and ribonuclease activity of IRE1, which splices mRNA to activate bZIP60...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29754956/measuring-endoplasmic-reticulum-signal-sequences-translocation-efficiency-using-the-xbp1-arrest-peptide
#16
Theresa Kriegler, Anastasia Magoulopoulou, Rocio Amate Marchal, Tara Hessa
Secretory proteins translocate across the mammalian ER membrane co-translationally via the ribosome-sec61 translocation machinery. Signal sequences within the polypeptide, which guide this event, are diverse in their hydrophobicity, charge, length, and amino acid composition. Despite the known sequence diversity in the ER signals, it is generally assumed that they have a dominant role in determining co-translational targeting and translocation process. We have analyzed co-translational events experienced by secretory proteins carrying efficient versus inefficient signal sequencing, using an assay based on Xbp1 peptide-mediated translational arrest...
May 3, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29743537/molecular-mechanism-of-er-stress-induced-pre-emptive-quality-control-involving-association-of-the-translocon-derlin-1-and-hrd1
#17
Hisae Kadowaki, Pasjan Satrimafitrah, Yasunari Takami, Hideki Nishitoh
The maintenance of endoplasmic reticulum (ER) homeostasis is essential for cell function. ER stress-induced pre-emptive quality control (ERpQC) helps alleviate the burden to a stressed ER by limiting further protein loading. We have previously reported the mechanisms of ERpQC, which includes a rerouting step and a degradation step. Under ER stress conditions, Derlin family proteins (Derlins), which are components of ER-associated degradation, reroute specific ER-targeting proteins to the cytosol. Newly synthesized rerouted polypeptides are degraded via the cytosolic chaperone Bag6 and the AAA-ATPase p97 in the ubiquitin-proteasome system...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740459/3d-structures-of-plant-phytochrome-a-as-pr-and-pfr-from-solid-state-nmr-implications-for-molecular-function
#18
Chen Song, Maria Andrea Mroginski, Christina Lang, Jakub Kopycki, Wolfgang Gärtner, Jörg Matysik, Jon Hughes
We present structural information for oat phyA3 in the far-red-light-absorbing (Pfr) signaling state, to our knowledge the first three-dimensional (3D) information for a plant phytochrome as Pfr. Solid-state magic-angle spinning (MAS) NMR was used to detect interatomic contacts in the complete photosensory module [residues 1-595, including the NTE (N-terminal extension), PAS ( P er/ A rnt/ S im), GAF (c G MP phosphodiesterase/ a denylyl cyclase/ F hlA) and PHY ( phy tochrome-specific) domains but with the C-terminal PAS repeat and transmitter-like module deleted] auto-assembled in vitro with 13 C- and 15 N-labeled phycocyanobilin (PCB) chromophore...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29733843/modulation-of-nuclear-factor-%C3%AE%C2%BAb-signaling-and-reduction-of-neural-tube-defects-by-quercetin-3-glucoside-in-embryos-of-diabetic-mice
#19
Chengyu Tan, Fantong Meng, E Albert Reece, Zhiyong Zhao
BACKGROUND: Diabetes mellitus in early pregnancy increases the risk of birth defects in infants. Maternal hyperglycemia stimulates the expression of nitric oxide (NO) synthase 2 (NOS2), which can be regulated by transcription factors of the nuclear factor-κB (NF-κB) family. Increases in reactive nitrogen species (RNS) generate intracellular stress conditions, including nitrosative, oxidative, and endoplasmic reticulum (ER) stresses, and trigger programmed cell death (or apoptosis) in the neural folds, resulting in neural tube defects (NTDs) in the embryo...
May 4, 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29729323/structure-of-the-dna-binding-domain-of-human-myelin-gene-regulatory-factor-reveals-its-potential-protein-dna-recognition-mode
#20
Baohua Chen, Yun Zhu, Sheng Ye, Rongguang Zhang
Myelin-gene regulatory factor (MYRF) is a membrane-bound transcription factors, which is responsible for the differentiation of oligodendrocytes and myelination of central nervous system. Followed by a self-cleavage by the intramolecular chaperone auto-processing (ICA) domain, DNA-binding domain (DBD) of MYRF is released from the endoplasmic reticulum (ER) and translocated to the nucleus to regulate gene expression. In present work, we have solved the crystal structure of the human MYRF-DBD to 1.85-Å resolution...
May 2, 2018: Journal of Structural Biology
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