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Jing Wang, Alina Fedoseienko, Bayou Chen, Ezra Burstein, Da Jia, Daniel D Billadeau
The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to maintain cellular homeostasis. Although retromer was originally described in yeast as a regulator of endosome-to-Golgi receptor recycling, mammalian retromer has emerged as a central player in endosome-to-plasma membrane recycling of a variety of receptors. Over the past decade, information regarding the mechanism by which retromer facilitates receptor trafficking has emerged, as has the identification of numerous retromer-associated molecules including the WASH complex, sorting nexins and TBC1d5...
April 18, 2018: Traffic
Renuka Kadirvelraj, Jeong-Yeh Yang, Justin H Sanders, Lin Liu, Annapoorani Ramiah, Pradeep Kumar Prabhakar, Geert-Jan Boons, Zachary A Wood, Kelley W Moremen
Asn-linked oligosaccharides are extensively modified during transit through the secretory pathway, first by trimming of the nascent glycan chains and subsequently by initiating and extending multiple oligosaccharide branches from the trimannosyl glycan core. Trimming and branching pathway steps are highly ordered and hierarchal based on the precise substrate specificities of the individual biosynthetic enzymes. A key committed step in the synthesis of complex-type glycans is catalyzed by N -acetylglucosaminyltransferase II (MGAT2), an enzyme that generates the second GlcNAcβ1,2- branch from the trimannosyl glycan core using UDP-GlcNAc as the sugar donor...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tianji Ma, Baiying Li, Ryan Wang, Pik Ki Lau, Yan Huang, Liwen Jiang, Randy Schekman, Yusong Guo
In planar cell polarity (PCP), the epithelial cells are polarized along the plane of the cell surface perpendicular to the classical apical-basal axis, a process mediated by several conserved signaling receptors. Two PCP-signaling proteins, VANGL planar cell-polarity protein 2 (Vangl2) and Frizzled6 (Fzd6), are located asymmetrically on opposite boundaries of the cell. Examining sorting of these two proteins at the trans-Golgi network (TGN), we demonstrated previously that the GTP-binding protein ADP ribosylation factor-related protein 1 (Arfrp1) and the clathrin adaptor complex 1 (AP-1) are required for Vangl2 transport from the TGN...
April 17, 2018: Journal of Biological Chemistry
Minhua Peng, Crystall Marie Dawn Swarbrick, Kitti Wing-Ki Chan, Dahai Luo, Wei Zhang, Xiaoping Lai, Geng Li, Subhash G Vasudevan
We previously showed that luteolin, a well-known plant-derived component found in the "heat clearing" class of Traditional Chinese Medicine (TCM) herbs, is an uncompetitive inhibitor (Ki 58.6 μM) of the host proprotein convertase furin, an endoprotease that is required for maturation of flaviviruses in the trans-Golgi compartment. Luteolin also weakly inhibited recombinant dengue virus NS2B/NS3 protease (Ki 140.36 μM) non-competitively. In order to further explore the mechanism of inhibition we isolated resistant mutants by continuous passaging of DENV2 in the presence of increasing concentrations of luteolin...
April 14, 2018: Antiviral Research
Yan Huang, Zhiping Hu
Cerebral ischemia/reperfusion-induced injury plays a significant role in the development of multi-subcellular organelles injury after ischemic stroke. UBIAD1 was discovered originally as a potential tumor suppressor protein. Recently, analysis of UBIAD1 has indicated it is a prenyltransferase enzyme for both non-mitochondrial CoQ10 and vitamin K2 production. Further, UBIAD1 has been localized to multiple subcellular organelles. Particularly, UBIAD1 plays an important role in the regulation of oxidative stress, apoptosis and cell proliferation, cholesterol and lipid metabolism, which was closely associated with the cerebral ischemic/reperfusion mechanism...
April 16, 2018: Journal of Cellular Physiology
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca S Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda C Herrmann, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
PURPOSE: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. Since multiple myeloma (MM) is derived from B cells, we investigated whether MM is also capable of PR1 cross-presentation and subsequently capable of being targeted using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Maxime Delos, François Foulquier, Charles Hellec, Dorothée Vicogne, Alexandre Fifre, Mathieu Carpentier, Dulce Papy-Garcia, Fabrice Allain, Agnès Denys
BACKGROUND: Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O-sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the same activity in vitro. They are however differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes. Here, we hypothesized that both isozymes might also display distinct subcellular localizations...
April 13, 2018: Biochimica et Biophysica Acta
Craig C Teerlink, Chad Huff, Jeff Stevens, Yao Yu, Sheri L Holmen, Mark R Silvis, Kirby Trombetti, Hua Zhao, Douglas Grossman, James M Farnham, Jingran Wen, Julio C Facelli, Alun Thomas, Markus Babst, Scott R Florell, Laurence Meyer, John J Zone, Sancy Leachman, Lisa A Cannon-Albright
Background: Statistically significant linkage of melanoma to chromosome 9q21 was previously reported in a Danish pedigree resource and independently confirmed in Utah high-risk pedigrees, indicating strong evidence that this region contains a melanoma predisposition gene. Methods: Whole-exome sequencing of pairs of related melanoma case subjects from two pedigrees with evidence of 9q21 linkage was performed to identify the responsible predisposition gene. Candidate variants were tested for association with melanoma in an independent set of 454 unrelated familial melanoma case subjects and 396 unrelated cancer-free control subjects from Utah, and 1534 melanoma case subjects and 1146 noncancer control subjects from Texas (MD Anderson) via a two-sided Fisher exact test...
April 11, 2018: Journal of the National Cancer Institute
Gaurav Barve, Priyadarshini Sanyal, Ravi Manjithaya
Autophagy is a vital conserved recycling process where eukaryotic cells remove unwanted proteins and organelles via lysosomal degradation and in turn, generate nutrients for the cells. The special feature of autophagy process is the formation of double-membrane vesicles called autophagosomes that engulf cellular cargo and deliver them to the vacuole or lysosomes for degradation. Inspite of more than 40 AuTophaGy (ATG) proteins and several organelles as known membrane source, autophagosome biogenesis is not entirely understood...
April 12, 2018: Current Genetics
Tayebeh Abedi, Mohamed Farouk Mohamed Khalil, Kanae Koike, Yoshio Hagura, Yuma Tazoe, Nobuhiro Ishida, Kenji Kitamura, Nobukazu Tanaka
We reported previously that tobacco plants transformed with the human UDP-galactose transporter 1 gene (hUGT1) had enhanced growth, displayed characteristic traits, and had an increased proportion of galactose (hyper-galactosylation) in the cell wall matrix polysaccharides. Here, we report that hUGT1-transgenic plants have an enhanced hardness. As determined by breaking and bending tests, the leaves and stems of hUGT1-transgenic plants were harder than those of control plants. Transmission electron microscopy revealed that the cell walls of palisade cells in leaves, and those of cortex cells and xylem fibers in stems of hUGT1-transgenic plants, were thicker than those of control plants...
April 9, 2018: Journal of Bioscience and Bioengineering
Moustafa Sakr, Xiao-Yan Li, Farideh Sabeh, Tamar Y Feinberg, John J G Tesmer, Yi Tang, Stephen J Weiss
Following ENU mutagenesis, a phenodeviant line was generated, termed the 'Cartoon mouse', that exhibits profound defects in growth and development. Cartoon mice harbor a single S466P point mutation in the MT1-MMP hemopexin domain, a 200 amino acid segment that is thought to play a critical role in regulating MT1-MMP collagenolytic activity. Herein, we demonstrate that the MT1-MMPS466P mutation replicates the phenotypic status of Mt1-mmp-null animals as well as the functional characteristics of MT1-MMP-/- cells...
April 11, 2018: Journal of Biological Chemistry
Nicola L Stevenson, Dylan J M Bergen, Amadeus Xu, Emily Wyatt, Freya Henry, Janine McCaughey, Laura Vuolo, Chrissy L Hammond, David J Stephens
Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies characterised by debilitating developmental defects affecting many tissues. Here we report a new role for regulator of calcineurin 2, RCAN2, in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing...
April 11, 2018: Journal of Cell Science
Xiuli Zhang, Xu Lian, Dan Liang, Lianzhi Zhang, Shengquan Liu, Lina Yang, Zhi-Hong Chi, Harvest F Gu
BACKGROUND/AIMS: Evidence from our and other groups has demonstrated that zinc transporter 7 in SLC30 family (ZnT7) inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in rat peritoneal mesothelial cells (RPMCs) under high glucose (HG) concentration. In the present study, we investigated the effect of ZnT7 on EMT of renal tubular epithelial cells (RTECs) in an in vitro model of diabetic nephropathy (DN). METHODS: A dual-fluorescent staining protocol was used for detection of ZnT7 in a normal rat kidney tubular epithelial cell line (NRK-52E cells)...
March 29, 2018: Kidney & Blood Pressure Research
Yohei Ishibashi, Makoto Ito, Yoshio Hirabayashi
Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2 ...
April 5, 2018: Biochemical and Biophysical Research Communications
C K Faccioli, R A Chedid, R H Mori, A D Do Amaral, I B F Vicentini, C A Vicentini
Membranous organelles, acid glycoconjugates and lipids were characterized in the digestive tract mucosa of Hemisorubim platyrhynchos by cytochemistry techniques. Two types of mucous-secreting cells were observed in the digestive tract epithelium: goblet cells in the oesophagus and intestine and epithelial cells in the stomach. These cells had a Golgi apparatus more developed than the other cell types. The cytochemical analysis revealed that secretory granules are reactive to acid glycoconjugates, varying in reaction intensity according to the region of the digestive tract...
April 6, 2018: Journal of Fish Biology
Linghuo Jiang, Dayong Xu, Ahsan Hameed, Tianshu Fang, Abu Bakr Ahmad Fazili, Faiza Asghar
Pmr1 is the Golgi/ER calcium pump, while Rch1 is a newly identified negative regulator of calcium influx in the plasma membrane of yeast cells. We show here that CaRch1 plays a dominant role over CaPmr1 in response of Candida albicans to SDS and tunicamycin stresses, while CaPmr1 has a major role in cell wall stress. Deletion of CaRCH1 increases the calcium/calcineurin signaling level in cells lacking CaPMR1. Calcineurin function is required for the role of CaRch1 in SDS stresses, while it is required for the function of CaPmr1 under all conditions examined...
April 2, 2018: Fungal Genetics and Biology: FG & B
Amer Ali Abd El-Hafeez, Toru Hosoi, Kanako Nakatsu, Mina Thon, Akira Shimamoto, Hidetoshi Tahara, Koichiro Ozawa
OBJECTIVE: The exposure of organelles, such as the endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes, to stress activates death mechanisms. Recently, telomerase reverse transcriptase (TERT) has been shown to be involved in cell survival. However, the relationship between TERT and the stress responses is still unclear. Here, we aimed to clarify the possible mechanisms of action through which TERT promotes cell survival by studying its effect on the stresses faced by multiple organelles in human fibroblasts...
April 5, 2018: Biotechnology Letters
Kou Motani, Hidetaka Kosako
Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-resident membrane protein that mediates cytosolic pathogen DNA-induced innate immunity and inflammatory responses in host defenses. STING is activated by cyclic di-nucleotides and is then translocated to the Golgi apparatus, an event that triggers STING assembly with the downstream enzyme TANK-binding kinase 1 (TBK1). This assembly leads to the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3), which, in turn, induces expression of type-I interferon (IFN) and chemokine genes...
April 4, 2018: Journal of Biological Chemistry
Philippe V Jutras, Marie-Claire Goulet, Pierre-Olivier Lavoie, Marc-André D'Aoust, Frank Sainsbury, Dominique Michaud
Cellular engineering approaches have been proposed to mitigate unintended proteolysis in plant protein biofactories, involving the design of protease activity-depleted environments by gene silencing or in situ inactivation with accessory protease inhibitors. Here, we assessed the impact of Influenza virus M2 proton channel on host protease activities and recombinant protein processing in the cell secretory pathway of Nicotiana benthamiana leaves. Transient co-expression assays with M2 and GFP variant pHluorin were first conducted to illustrate the potential of proton export from the Golgi lumen to promote recombinant protein yield...
April 4, 2018: Plant Biotechnology Journal
Qin-Peng Yang, Ming-Fen Fu, Hao Gao, Kazuo Yamamoto, Dan Hu, Sheng-Ying Qin
Malectin is a newly discovered endoplasmic reticulum (ER)-resident lectin, which specifically recognizes Glc2Man9GlcNAc2 on newly synthesized glycoproteins. We have previously demonstrated that malectin forms a complex with ribophorin I for selective retention of misfolded glycoproteins inside the cell. Here, we showed that ribophorin I also functions to regulate the subcellular localization of malectin under various conditions. Even though malectin does not contain an ER-retention signal motif, we found that endogenous malectin mainly localizes in the ER, which is disrupted upon suppression of ribophorin I, leading to its movement from ER to Golgi...
April 2, 2018: Glycobiology
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