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coatomer protein

Eleftherios Karanasios, Simon A Walker, Hanneke Okkenhaug, Maria Manifava, Eric Hummel, Hans Zimmermann, Qashif Ahmed, Marie-Charlotte Domart, Lucy Collinson, Nicholas T Ktistakis
Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery...
August 11, 2016: Nature Communications
Kosuke Izumi, Maggie Brett, Eriko Nishi, Séverine Drunat, Ee-Shien Tan, Katsunori Fujiki, Sophie Lebon, Breana Cham, Koji Masuda, Michiko Arakawa, Adeline Jacquinet, Yusuke Yamazumi, Shu-Ting Chen, Alain Verloes, Yuki Okada, Yuki Katou, Tomohiko Nakamura, Tetsu Akiyama, Pierre Gressens, Roger Foo, Sandrine Passemard, Ene-Choo Tan, Vincent El Ghouzzi, Katsuhiko Shirahige
Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex...
August 4, 2016: American Journal of Human Genetics
Shengliu Wang, Yujia Zhai, Xiaoyun Pang, Tongxin Niu, Yue-He Ding, Meng-Qiu Dong, Victor W Hsu, Zhe Sun, Fei Sun
Studies on coat protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting...
August 2016: Protein & Cell
Miharu Maeda, Kota Saito, Toshiaki Katada
Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER...
September 1, 2016: Molecular Biology of the Cell
Jordy J Hsiao, Melinda M Smits, Brandon H Ng, Jinhee Lee, Michael E Wright
Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the "AR-interactome." Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR)...
September 2, 2016: Journal of Biological Chemistry
Eric C Arakel, Kora P Richter, Anne Clancy, Blanche Schwappach
Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
Timothy J Vece, Levi B Watkin, Sarah K Nicholas, Debra Canter, Michael C Braun, Robert Paul Guillerman, Karen W Eldin, Grant Bertolet, Scott D McKinley, Marietta de Guzman, Lisa R Forbes, Ivan Chinn, Jordan S Orange
Inherently defective immunity typically results in either ineffective host defense, immune regulation, or both. As a category of primary immunodeficiency diseases, those that impair immune regulation can lead to autoimmunity and/or autoinflammation. In this review we focus on one of the most recently discovered primary immunodeficiencies that leads to immune dysregulation: "Copa syndrome". Copa syndrome is named for the gene mutated in the disease, which encodes the alpha subunit of the coatomer complex-I that, in aggregate, is devoted to transiting molecular cargo from the Golgi complex to the endoplasmic reticulum (ER)...
May 2016: Journal of Clinical Immunology
Mohammed Bensellam, Emma L Maxwell, Jeng Yie Chan, Jude Luzuriaga, Phillip K West, Jean-Christophe Jonas, Jenny E Gunton, D Ross Laybutt
AIMS/HYPOTHESIS: Hypoxia may contribute to beta cell failure in type 2 diabetes and islet transplantation. The adaptive unfolded protein response (UPR) is required for endoplasmic reticulum (ER) homeostasis. Here we investigated whether or not hypoxia regulates the UPR in beta cells and the role the adaptive UPR plays during hypoxic stress. METHODS: Mouse islets and MIN6 cells were exposed to various oxygen (O2) tensions. DNA-damage inducible transcript 3 (DDIT3), hypoxia-inducible transcription factor (HIF)1α and HSPA5 were knocked down using small interfering (si)RNA; Hspa5 was also overexpressed...
July 2016: Diabetologia
Alberto Canfrán-Duque, Luis C Barrio, Milagros Lerma, Gema de la Peña, Jorge Serna, Oscar Pastor, Miguel A Lasunción, Rebeca Busto
First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL...
2016: International Journal of Molecular Sciences
Weilie Ma, Margarita Lin, Hang Ding, Guorong Lin, Zhizhen Zhang
OBJECTIVE: HDL and its apolipoproteins protect against atherosclerotic disease partly by removing excess cholesterol from macrophage foam cells. But the underlying mechanisms of cholesterol clearance are still not well defined. We investigated roles of vesicle trafficking of coatomer β-COP in delivering cholesterol to the cell surface during apoA-1 and apoE-mediated lipid efflux from fibroblasts and THP-1 macrophages. METHODS: shRNA knockout, confocal and electron microscopy and biochemical analysis were used to investigate the roles of β-COP in apolipoprotein-mediated cholesterol efflux in fibroblasts and THP-1 macrophages...
2016: PloS One
Sang-Hee Lee, Eun-Ji Song, Yong Hwangbo, Seunghyung Lee, Choon-Keun Park
The aim of this study was to examine protein expression patterns of uterine histroph (UH) during the follicular phase (FP) and luteal phase (LP) in pigs. Forty-nine common proteins were identified from FP and LP samples; five were significantly down-regulated (>1.5-fold), while 15 were significantly up-regulated (>1.5-fold) in LPUH compared with FPUH (P<0.05). The 20 differentially-expressed proteins are involved in cell proliferation, cell responses, translation, transport, and metabolism and their molecular functions include nucleic acid binding, oxygen activity, enzymatic activity, growth activity, iron binding, and redox binding...
May 2016: Animal Reproduction Science
Vasilis J Promponas, Katerina R Katsani, Benjamin J Blencowe, Christos A Ouzounis
Eukaryotic cells are defined by compartments through which the trafficking of macromolecules is mediated by large complexes, such as the nuclear pore, transport vesicles and intraflagellar transport. The assembly and maintenance of these complexes is facilitated by endomembrane coatomers, long suspected to be divergently related on the basis of structural and more recently phylogenomic analysis. By performing supervised walks in sequence space across coatomer superfamilies, we uncover subtle sequence patterns that have remained elusive to date, ultimately unifying eukaryotic coatomers by divergent evolution...
2016: Scientific Reports
Masaoki Takano, Mieko Otani, Takahiro Kaji, Keiji Sano, Michiko Hamada-Kanazawa, Shogo Matsuyama
OBJECTIVES: Choroid plexus (CP) epithelial cells have multiple functions in the cerebral ventricles, including cerebrospinal fluid (CSF) production and forming part of the blood-CSF barrier. They are also responsible for producing inflammatory mediators involved in meningitis. The present study aimed to elucidate the functions of the CP epithelial cells during CNS inflammation. MATERIALS AND METHODS: We analyzed the proteome and phosphoproteome in lipid A-treated ECPC-4 mouse CP cells by gel electrophoresis and mass spectrometry...
April 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Diego Iglesias-Gato, Pernilla Wikström, Stefka Tyanova, Charlotte Lavallee, Elin Thysell, Jessica Carlsson, Christina Hägglöf, Jürgen Cox, Ove Andrén, Pär Stattin, Lars Egevad, Anders Widmark, Anders Bjartell, Colin C Collins, Anders Bergh, Tamar Geiger, Matthias Mann, Amilcar Flores-Morales
BACKGROUND: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries. OBJECTIVES: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness...
May 2016: European Urology
Si-Ming Zhang, Sarah K Buddenborg, Coen M Adema, John T Sullivan, Eric S Loker
In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy-based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails...
2015: PLoS Neglected Tropical Diseases
Hee-Kyung Ahn, Yong Won Kang, Hye Min Lim, Inhwan Hwang, Hyun-Sook Pai
COPI vesicles are essential to the retrograde transport of proteins in the early secretory pathway. The COPI coatomer complex consists of seven subunits, termed α-, β-, β'-, γ-, δ-, ε-, and ζ-COP, in yeast and mammals. Plant genomes have homologs of these subunits, but the essentiality of their cellular functions has hampered the functional characterization of the subunit genes in plants. Here we have employed virus-induced gene silencing (VIGS) and dexamethasone (DEX)-inducible RNAi of the COPI subunit genes to study the in vivo functions of the COPI coatomer complex in plants...
October 2015: Molecules and Cells
Cheuk Hang Woo, Caiji Gao, Ping Yu, Linna Tu, Zhaoyue Meng, David K Banfield, Xiaoqiang Yao, Liwen Jiang
We recently identified a new COPI-interacting KXD/E motif in the C-terminal cytosolic tail (CT) of Arabidopsis endomembrane protein 12 (AtEMP12) as being a crucial Golgi retention mechanism for AtEMP12. This KXD/E motif is conserved in CTs of all EMPs found in plants, yeast, and humans and is also present in hundreds of other membrane proteins. Here, by cloning selective EMP isoforms from plants, yeast, and mammals, we study the localizations of EMPs in different expression systems, since there are contradictory reports on the localizations of EMPs...
November 15, 2015: Molecular Biology of the Cell
Jeffrey D Covington, Robert C Noland, R Caitlin Hebert, Blaine S Masinter, Steven R Smith, Arild C Rustan, Eric Ravussin, Sudip Bajpeyi
CONTEXT: The role of perilipin 3 (PLIN3) on lipid oxidation is not fully understood. OBJECTIVE: We aimed to 1) determine whether skeletal muscle PLIN3 protein content is associated with lipid oxidation in humans, 2) understand the role of PLIN3 in lipid oxidation by knocking down PLIN3 protein content in primary human myotubes, and 3) compare PLIN3 content and its role in lipid oxidation in human primary skeletal muscle cultures established from sedentary, healthy lean (leans), type 2 diabetic (T2D), and physically active donors...
October 2015: Journal of Clinical Endocrinology and Metabolism
Avital Lahav, Haim Rozenberg, Anna Parnis, Dan Cassel, Noam Adir
The heptameric COPI coat (coatomer) plays an essential role in vesicular transport in the early secretory system of eukaryotic cells. While the structures of some of the subunits have been determined, that of the δ-COP subunit has not been reported to date. The δ-COP subunit is part of a subcomplex with structural similarity to tetrameric clathrin adaptors (APs), where δ-COP is the structural homologue of the AP μ subunit. Here, the crystal structure of the μ homology domain (MHD) of δ-COP (δ-MHD) obtained by phasing using a combined SAD-MR method is presented at 2...
June 2015: Acta Crystallographica. Section D, Biological Crystallography
Ben Dorshorst, Corneliu Henegar, Xiaoping Liao, Markus Sällman Almén, Carl-Johan Rubin, Shosuke Ito, Kazumasa Wakamatsu, Paul Stothard, Brian Van Doormaal, Graham Plastow, Gregory S Barsh, Leif Andersson
Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle...
2015: PloS One
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