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Amita Gorur, Lin Yuan, Samuel J Kenny, Satoshi Baba, Ke Xu, Randy Schekman
The coat protein complex II (COPII) is essential for the transport of large cargo, such as 300-nm procollagen I (PC1) molecules, from the endoplasmic reticulum (ER) to the Golgi. Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles at ER exit sites to more than 300 nm in diameter and accelerates the secretion of PC1. However, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated. In this study, using stochastic optical reconstruction microscopy, correlated light electron microscopy, and live-cell imaging, we demonstrate the existence of mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are physically separated from ER...
April 20, 2017: Journal of Cell Biology
Francisco F Rodrigues, Tony J C Harris
Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis...
April 14, 2017: Small GTPases
Emilie M Outzen, Marina Zaki, Rahila Mehryar, Bahareh Abdolalizadeh, Waseem Sajid, Harrie C M Boonen, Anette Sams, Majid Sheykhzade
Angiotensin II (Ang II) might induce pro-inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro-inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance-sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24-hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL-6 or MCP-1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine...
April 2017: Basic & Clinical Pharmacology & Toxicology
Yihua Wang, Feng Liu, Yulong Ren, Yunlong Wang, Xi Liu, Wuhua Long, Di Wang, Jianping Zhu, Xiaopin Zhu, Ruonan Jing, Mingming Wu, Yuanyuan Hao, Ling Jiang, Chunming Wang, Haiyang Wang, Yiqun Bao, Jianmin Wan
Coat protein complex II (COPII) mediates the first step of anterograde transport of newly synthesized proteins from the endoplasmic reticulum (ER) to other endomembrane compartments in eukaryotes. A group of evolutionarily conserved proteins (Sar1, Sec23, Sec24, Sec13, and Sec31) constitutes the basic COPII coat machinery; however, the details of how the COPII coat assembly is regulated remain unclear. Here, we report a protein transport mutant of rice (Oryza sativa), named glutelin precursor accumulation4 (gpa4), which accumulates 57-kD glutelin precursors and forms two types of ER-derived abnormal structures...
November 2016: Plant Cell
Khuthala Mnika, Gift D Pule, Collet Dandara, Ambroise Wonkam
Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids...
October 2016: Omics: a Journal of Integrative Biology
Jennifer A Dickens, Adriana Ordóñez, Joseph E Chambers, Alison J Beckett, Vruti Patel, Elke Malzer, Caia S Dominicus, Jayson Bradley, Andrew A Peden, Ian A Prior, David A Lomas, Stefan J Marciniak
α1-Antitrypsin is a serine protease inhibitor produced in the liver that is responsible for the regulation of pulmonary inflammation. The commonest pathogenic gene mutation yields Z-α1-antitrypsin, which has a propensity to self-associate forming polymers that become trapped in inclusions of endoplasmic reticulum (ER). It is unclear whether these inclusions are connected to the main ER network in Z-α1-antitrypsin-expressing cells. Using live cell imaging, we found that despite inclusions containing an immobile matrix of polymeric α1-antitrypsin, small ER resident proteins can diffuse freely within them...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
N V Kirbaeva, N E Sharanova, V M Zhminchenko, I Yu Toropygin, E V Koplik, S S Pertsov, A V Vasil'ev
Differences in the proteomic profiles of the brain amygdala in rats with different prognostic resistance to stress were found on the model of metabolic stress. Differential expression of tropomodulin-2, GTP-binding protein SAR1, peroxiredoxin-2, calcineurin B homologous protein 1, Ras-related protein Rab-14, glutathione S-transferase omega-1, Tcrb protein, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (mitochondrial) was shown to depend on the behavioral pattern of animals and stage of the study...
August 2016: Bulletin of Experimental Biology and Medicine
Yoji Yonemura, Xiaolin Li, Katja Müller, Andreas Krämer, Paul Atigbire, Torben Mentrup, Talitha Feuerhake, Torsten Kroll, Olga Shomron, Richard Nohl, Hans-Dieter Arndt, Christian Hoischen, Peter Hemmerich, Koret Hirschberg, Christoph Kaether
Export out of the endoplasmic reticulum (ER) involves the Sar1 and COPII machinery acting at ER exit sites (ERES). Whether and how cargo proteins are recruited upstream of Sar1 and COPII is unclear. Two models are conceivable, a recruitment model where cargo is actively transported through a transport factor and handed over to the Sar1 and COPII machinery in ERES, and a capture model, where cargo freely diffuses into ERES where it is captured by the Sar1 and COPII machinery. Using the novel secretion inhibitor FLI-06, we show that recruitment of the cargo VSVG to ERES is an active process upstream of Sar1 and COPII...
October 15, 2016: Journal of Cell Science
Wenfu Ma, Jonathan Goldberg
The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yuan Fan, Tian Ge, Yanli Zheng, Hua Li, Fangqin Cheng
Soil salinization has become a worldwide problem that imposes restrictions on crop production and food quality. This study utilizes a soil column experiment to address the potential of using mixed solid waste (vinegar residue, fly ash, and sewage sludge) as soil amendment to ameliorate saline-sodic soil and enhance crop growth. Mixed solid waste with vinegar residue content ranging from 60-90 %, sewage sludge of 8.7-30 %, and fly ash of 1.3-10 % was added to saline-sodic soil (electrical conductivity (EC1:5) = 1...
November 2016: Environmental Science and Pollution Research International
Kazuo Kurokawa, Yasuyuki Suda, Akihiko Nakano
The Sar1 GTPase controls coat assembly on coat protein complex II (COPII)-coated vesicles, which mediate protein transport from the endoplasmic reticulum (ER) to the Golgi. The GTP-bound form of Sar1, activated by the ER-localized guanine nucleotide exchange factor (GEF) Sec12, associates with the ER membrane. GTP hydrolysis by Sar1, stimulated by the COPII-vesicle-localized GTPase-activating protein (GAP) Sec23, in turn causes Sar1 to dissociate from the membrane. Thus, Sar1 is cycled between active and inactive states, and on and off vesicle membranes, but its precise spatiotemporal regulation remains unknown...
September 1, 2016: Journal of Cell Science
Kin Pan Chung, Yonglun Zeng, Liwen Jiang
In eukaryotes, the best-described mechanism of endoplasmic reticulum (ER) export is mediated by coat protein complex II (COPII) vesicles, which comprise five conserved cytosolic components [secretion-associated, Ras-related protein 1 (Sar1), Sec23-24, and Sec13-31]. In higher organisms, multiple paralogs of COPII components are created due to gene duplication. However, the functional diversity of plant COPII subunit isoforms remains largely elusive. Here we summarize and discuss the latest findings derived from studies of various arabidopsis COPII subunit isoforms and their functional diversity...
September 2016: Trends in Plant Science
Agnese Petrera, Johann Gassenhuber, Sven Ruf, Deepika Gunasekaran, Jennifer Esser, Jasmin Hasmik Shahinian, Thomas Hübschle, Hartmut Rütten, Thorsten Sadowski, Oliver Schilling
BACKGROUND: Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure. METHODS: Mice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post-surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo...
2016: Journal of Translational Medicine
Zheng Li, Qianqian Qiu, Xinqian Geng, Jianyong Yang, Wenlong Huang, Hai Qian
INTRODUCTION: The alarming prevalence of type 2 diabetes mellitus (T2DM) stimulated the exploitation of new antidiabetic drugs with extended durability and enhanced safety. In this regard, the free fatty acid receptor 1 (FFA1) and FFA4 have emerged as attractive targets in the last decade. FFA1 has prominent advantages in promoting insulin and incretin secretion while FFA4 shows great potential in incretin secretion, insulin sensitization and anti-inflammatory effects. AREA COVERED: Herein, the authors focus specifically on FFA1 and FFA4 agonists in clinical trials and preclinical development...
August 2016: Expert Opinion on Investigational Drugs
Tomoya Tanabe, Miharu Maeda, Kota Saito, Toshiaki Katada
Two independent functions of cTAGE5 have been reported in collagen VII export from the endoplasmic reticulum (ER). cTAGE5 not only forms a cargo receptor complex with TANGO1, but it also acts as a scaffold to recruit Sec12, a guanine-nucleotide exchange factor for Sar1 GTPase, to ER exit sites. However, the relationship between the two functions remains unclear. Here we isolated point mutants of cTAGE5 that lost Sec12-binding ability but retained binding to TANGO1. Although expression of the mutant alone could not rescue the defects in collagen VII secretion mediated by cTAGE5 knockdown, coexpression with Sar1, but not with the GTPase-deficient mutant, recovered secretion...
July 1, 2016: Molecular Biology of the Cell
J A Abecia, P Chemineau, A Gómez, M Keller, F Forcada, J A Delgadillo
The objective of this study was to determine the effect of sexually activated (by specific photoperiodic treatments) vasectomized rams on the onset of puberty in autumn-born ewe lambs in spring. Photoperiodic-treated rams were assigned to one of three groups, which were sequentially exposed to two months of long days (16h light/d) and given three melatonin implants at the end of the long days (sexually-activated-rams; SAR): SAR1 (n=5; 1 December-31 January), SAR2 (n=5; 1 Jan-28 February), and SAR3 (n=5; 1 February-31 March)...
July 2016: Animal Reproduction Science
Karin B Ackema, Cristina Prescianotto-Baschong, Jürgen Hench, Shyi Chyi Wang, Zhi Hui Chia, Heidi Mergentaler, Fredéric Bard, Stephan Frank, Anne Spang
Endoplasmic reticulum (ER)-mitochondrial contact sites play a pivotal role in exchange of lipids and ions between the two organelles. How size and function of these contact sites are regulated remains elusive. Here we report a previously unanticipated, but conserved role of the small GTPase Sar1 in the regulation of ER-mitochondrial contact site size. Activated Sar1 introduces membrane curvature through its N-terminal amphiphatic helix at the ER-mitochondria interphase and thereby reducing contact size. Conversely, the S...
2016: PloS One
Carine de Marcos Lousa, Eric Soubeyrand, Paolo Bolognese, Valerie Wattelet-Boyer, Guillaume Bouyssou, Claireline Marais, Yohann Boutté, Francesco Filippini, Patrick Moreau
SNARE proteins are central elements of the machinery involved in membrane fusion of eukaryotic cells. In animals and plants, SNAREs have diversified to sustain a variety of specific functions. In animals, R-SNARE proteins called brevins have diversified; in contrast, in plants, the R-SNARE proteins named longins have diversified. Recently, a new subfamily of four longins named 'phytolongins' (Phyl) was discovered. One intriguing aspect of Phyl proteins is the lack of the typical SNARE motif, which is replaced by another domain termed the 'Phyl domain'...
March 9, 2016: Journal of Experimental Botany
Liling Wang, Haibo Li, Yifeng Zhou, Yuchuan Qin, Yanbin Wang, Bentong Liu, Hua Qian
ADP-ribosylation factor 6 (ARF6) is an evolutionarily conserved molecule that has an essential function in intracellular trafficking and organelle structure. To better understand its role during presymbiosis between plant roots and compatible filamentous fungi, the full-length cDNA sequence of ARF6 from Pisolithus tinctorius was cloned and a variety of bioinformatics analyses performed. The full-length sequence was 849 bp long and contained a 549 bp open reading frame encoding a protein of 182 amino acids. A phylogenetic analysis showed that ptARF6 was the ortholog of the ADP ribosylation factor 6/GTPase SAR1 gene from the white-rot basidiomycete Trametes versicolor...
May 2016: Canadian Journal of Microbiology
Junpei Norisada, Yoko Hirata, Fumimasa Amaya, Kazutoshi Kiuchi, Kentaro Oh-hashi
Cerebral dopamine neurotrophic factor (CDNF) is a paralogous protein of mesencephalic astrocyte-derived neurotrophic factor (MANF). Both proteins have been reported to show a common cytoprotective effect on dopaminergic neurons as a secretory protein containing the KDEL-like motif of the ER retrieval signal at the C-terminus, RTDL in MANF and [Q/K]TEL in CDNF among many species, although functions of paralogous proteins tend to differ from each other. In this study, we focused on post-translational regulations of their retention in the endoplasmic reticulum (ER) and secretion and performed comparative experiments on characterization of mouse MANF and mouse CDNF according to our previous report about biosynthesis and secretion of mouse MANF using a NanoLuc system...
2016: PloS One
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