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https://www.readbyqxmd.com/read/28339924/the-trans-golgi-network-and-the-golgi-stacks-behave-independently-during-regeneration-after-brefeldin-a-treatment-in-tobacco-by-2-cells
#1
Yoko Ito, Kiminori Toyooka, Masaru Fujimoto, Takashi Ueda, Tomohiro Uemura, Akihiko Nakano
The trans-Golgi network (TGN) plays an essential role in intracellular membrane trafficking. In plant cells, recent live-cell imaging studies have revealed the dynamic behavior of the TGN independent from the Golgi apparatus. In order to better understand the relationships between the two organelles, we examined their dynamic responses to the reagent brefeldin A (BFA) and their recovery after BFA removal. Golgi markers responded to BFA similarly over a range of concentrations, whereas the behavior of the TGN was BFA concentration dependent...
February 21, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28334785/amino-acid-substitution-equivalent-to-human-chorea-acanthocytosis-i2771r-in-yeast-vps13-protein-affects-its-binding-to-phosphatidylinositol-3-phosphate
#2
Weronika Rzepnikowska, Krzysztof Flis, Joanna Kaminska, Marcin Grynberg, Agnieszka Urbanek, Kathryn R Ayscough, Teresa Zoladek
The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. The hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) in the membranes of neuronal cells. Yeast Vps13 is involved in vacuolar protein transport and, like hVps13A, participates in PI4P metabolism. Vps13 proteins are conserved in eukaryotes, but their molecular function remains unknown. One of the mutations found in ChAc patients causes amino acids substitution I2771R which affects the localization of hVps13A in skeletal muscles...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331092/monkeypox-virus-host-factor-screen-in-haploid-cells-identifies-essential-role-of-garp-complex-in-extracellular-virus-formation
#3
Susan Realegeno, Andreas S Puschnik, Amrita Kumar, Cynthia Goldsmith, Jillybeth Burgado, Suryaprakash Sambhara, Victoria A Olson, Darin Carroll, Inger Damon, Tetsuya Hirata, Taroh Kinoshita, Jan E Carette, Panayampalli Subbian Satheshkumar
Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis and glycosylphosphatidylinositol (GPI) - anchor biosynthesis...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28325841/an-inducible-amphipathic-helix-within-the-intrinsically-disordered-c-terminus-is-not-required-for-protein-biosynthesis-trafficking-or-garp2-interaction-but-can-participate-in-membrane-curvature-generation-by-peripherin-2-rds
#4
Michelle L Milstein, Victoria A Kimler, Chiranjib Ghatak, Alexey S Ladokhin, Andrew F X Goldberg
Peripherin-2/rds is required for biogenesis of vertebrate photoreceptor outer segment organelles. Its localization at the high curvature rim domains of outer segment disk membranes suggests that it may act to shape these structures; however, the molecular function of this protein is not yet resolved. Here, we apply biochemical, biophysical, and imaging techniques, to elucidate the role(s) played by the protein's intrinsically disordered C-terminal domain, and an incipient amphipathic α-helix contained within it...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28325821/phosphorylation-of-the-exocyst-protein-exo84-by-tbk1-promotes-insulin-stimulated-glut4-trafficking
#5
Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R Saltiel
Insulin stimulates glucose uptake through the translocation of the glucose transporter GLUT4 to the plasma membrane. The exocyst complex tethers GLUT4-containing vesicles to the plasma membrane, a process that requires the binding of the G protein (heterotrimeric guanine nucleotide-binding protein) RalA to the exocyst complex. We report that upon activation of RalA, the protein kinase TBK1 phosphorylated the exocyst subunit Exo84. Knockdown of TBK1 blocked insulin-stimulated glucose uptake and GLUT4 translocation; knockout of TBK1 in adipocytes blocked insulin-stimulated glucose uptake; and ectopic overexpression of a kinase-inactive mutant of TBK1 reduced insulin-stimulated glucose uptake in 3T3-L1 adipocytes...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28324651/line-activity-of-ganglioside-gm1-regulates-raft-size-distribution-in-a-cholesterol-dependent-manner
#6
Timur R Galimzyanov, Anna S Lyushnyak, Veronika V Aleksandrova, Liudmila A Shilova, Ilya I Mikhalyov, Irina M Molotkovskaya, Sergey A Akimov, Oleg V Batishchev
Liquid-ordered lipid domains, also called rafts, are assumed to be important players in different cellular processes, mainly signal transduction and membrane trafficking. They are thicker than the disordered part of the membrane and are thought to form for compensating the hydrophobic mismatch between transmembrane proteins and lipid environment. Despite the existence of such structures in vivo is still an open question, they are observed in model systems of multicomponent lipid bilayers. Moreover, the predictions obtained from model experiments allow explaining different physiological processes possibly involving rafts...
March 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28324111/arap1-deficiency-causes-photoreceptor-degeneration-in-mice
#7
Ala Moshiri, Devin Humpal, Brian C Leonard, Denise M Imai, Addy Tham, Lynette Bower, Dave Clary, Thomas M Glaser, K C Kent Lloyd, Christopher J Murphy
Purpose: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Methods: Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324000/trh-action-is-impaired-in-pituitaries-of-male-igsf1-deficient-mice
#8
Marc-Olivier Turgeon, Tanya L Silander, Denica Doycheva, Xiao-Hui Liao, Marc Rigden, Luisina Ongaro, Xiang Zhou, Sjoerd D Joustra, Jan M Wit, Mike G Wade, Heike Heuer, Samuel Refetoff, Daniel J Bernard
Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene cause central hypothyroidism. IGSF1 is a transmembrane glycoprotein of unknown function expressed in TSH-producing thyrotrope cells of the anterior pituitary gland. The protein is co-translationally cleaved, with only its C-terminal domain (CTD) being trafficked to the plasma membrane. Most intragenic IGSF1 mutations in humans map to the CTD. Here, we used CRISPR-Cas9 to introduce a loss-of-function mutation into the IGSF1-CTD in mice...
January 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322444/identification-and-characterization-of-site-specific-n-glycosylation-in-the-potassium-channel-kv3-1b
#9
Paul Christian Vicente, Jin Young Kim, Jeong-Ju Ha, Min-Young Song, Hyun-Kyung Lee, Dong-Hyun Kim, Jin-Sung Choi, Kang-Sik Park
The potassium ion channel Kv3.1b is a member of a family of voltage-gated ion channels that are glycosylated in their mature form. In the present study, we demonstrate the impact of N-glycosylation at specific asparagine residues on the trafficking of the Kv3.1b protein. Large quantities of asparagine 229 (N229)-glycosylated Kv3.1b reached the plasma membrane, whereas N220-glycosylated and unglycosylated Kv3.1b were mainly retained in the endoplasmic reticulum (ER). These ER-retained Kv3.1b proteins were susceptible to degradation when co-expressed with calnexin, whereas Kv3...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28321204/a-comprehensive-view-of-the-%C3%AE-arrestinome
#10
Pascale Crépieux, Anne Poupon, Nathalie Langonné-Gallay, Eric Reiter, Javier Delgado, Martin H Schaefer, Thomas Bourquard, Luis Serrano, Christina Kiel
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28320834/early-intracellular-trafficking-of-granulibacter-bethesdensis-in-human-macrophages
#11
Jessica Chu, Margery G Smelkinson, David W Dorward, Kol A Zarember, John I Gallin
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that bacteriostatic activity of monocyte derived macrophages (MDM) requires NOX2 and IFNγ-pretreatment. To determine if G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320825/structure-of-the-rzz-complex-and-molecular-basis-of-its-interaction-with-spindly
#12
Shyamal Mosalaganti, Jenny Keller, Anika Altenfeld, Michael Winzker, Pascaline Rombaut, Michael Saur, Arsen Petrovic, Annemarie Wehenkel, Sabine Wohlgemuth, Franziska Müller, Stefano Maffini, Tanja Bange, Franz Herzog, Herbert Waldmann, Stefan Raunser, Andrea Musacchio
Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific ≈800-kD ROD-Zwilch-ZW10 (RZZ) complex builds a fibrous corona that assembles on mitotic kinetochores before MT attachment to promote chromosome alignment and robust spindle assembly checkpoint signaling. In this study, we combine biochemical reconstitutions, single-particle electron cryomicroscopy, cross-linking mass spectrometry, and structural modeling to build a complete model of human RZZ...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28318354/hs1bp3-inhibits-autophagy-by-regulation-of-pld1
#13
Kristiane Søreng, Helene Knævelsrud, Petter Holland, Anne Simonsen
Macroautophagy/autophagy is a membrane trafficking and intracellular degradation process involving the formation of double-membrane autophagosomes and their ultimate fusion with lysosomes. Much is yet to be learned about the regulation of this process, especially at the level of the membranes and lipids involved. We have recently found that the PX domain protein HS1BP3 (HCLS1 binding protein 3) is a negative regulator of autophagosome formation. HS1BP3 depletion increases the formation of LC3-positive autophagosomes both in human cells and zebrafish...
February 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28317099/mutations-in-ergic1-cause-arthrogryposis-multiplex-congenita-neuropathic-type
#14
Eyal Reinstein, Valerie Dersinover, Rona Lotan, Meital Gal-Tanhami, Inbal Bulokin Nachman, Eran Eyal, Jaber Lutfi, Nurit Magal, Mordechai Shohat
Arthrogryposis multiplex congenita (AMC) is heterogeneous group of disorders characterized by non-progressive joint contractures from birth that involve more than one part of the body. There are various etiologies for AMC including genetic and environmental depends on the specific type, however, for most types, the cause is not fully understood. We previously reported large Israeli Arab kindred consisting of 16 patients affected with AMC neuropathic type, and mapped the locus to a 5.5 cM interval on chromosome 5qter...
March 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28317021/the-bloc-1-subunit-pallidin-facilitates-activity-dependent-synaptic-vesicle-recycling
#15
Xun Chen, Wenpei Ma, Shixing Zhang, Jeremy Paluch, Wanlin Guo, Dion K Dickman
Membrane trafficking pathways must be exquisitely coordinated at synaptic terminals to maintain functionality, particularly during conditions of high activity. We have generated null mutations in the Drosophila homolog of pallidin, a central subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), to determine its role in synaptic development and physiology. We find that Pallidin localizes to presynaptic microtubules and cytoskeletal structures, and that the stability of Pallidin protein is highly dependent on the BLOC-1 components Dysbindin and Blos1...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28303263/astrocyte-ca-2-influx-negatively-regulates-neuronal-activity
#16
Yao V Zhang, Kiel G Ormerod, J Troy Littleton
Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca(2+) signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca(2+) oscillatory activity manifested by fast, recurrent microdomain Ca(2+) fluctuations within processes that infiltrate the synaptic neuropil...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28303090/the-inhibitory-effect-of-%C3%AE-%C3%AE-hydrolase-domain-containing-6-abhd6-on-the-surface-targeting-of-glua2-and-glua3-containing-ampa-receptors
#17
Mengping Wei, Moye Jia, Jian Zhang, Lulu Yu, Yunzhi Zhao, Yingqi Chen, Yimeng Ma, Wei Zhang, Yun S Shi, Chen Zhang
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control the biosynthesis, membrane trafficking, and synaptic targeting of AMPARs. Our previous report showed that α/β-hydrolase domain-containing 6 (ABHD6), an auxiliary subunit for AMPARs, suppresses the membrane delivery and function of GluA1-containing receptors in both heterologous cells and neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28300864/whole-exome-sequencing-in-the-framingham-heart-study-identifies-rare-variation-in-hyal2-that-influences-platelet-aggregation
#18
John D Eicher, Ming-Huei Chen, Achilleas N Pitsillides, Honghuang Lin, Narayanan Veeraraghavan, Jennifer A Brody, Ginger A Metcalf, Donna M Muzny, Richard A Gibbs, Diane M Becker, Lewis C Becker, Nauder Faraday, Rasika A Mathias, Lisa R Yanek, Eric Boerwinkle, L Adrienne Cupples, Andrew D Johnson
Inhibition of platelet reactivity is a common therapeutic strategy in secondary prevention of cardiovascular disease. Genetic and environmental factors influence inter-individual variation in platelet reactivity. Identifying genes that contribute to platelet reactivity can reveal new biological mechanisms and possible therapeutic targets. Here, we examined rare coding variation to identify genes associated with platelet reactivity in a population-based cohort. To do so, we performed whole exome sequencing in the Framingham Heart Study and conducted single variant and gene-based association tests against platelet reactivity to collagen, adenosine diphosphate (ADP), and epinephrine agonists in up to 1,211 individuals...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28300646/developmental-changes-in-trak-mediated-mitochondrial-transport-in-neurons
#19
Omar Loss, F Anne Stephenson
Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites...
March 11, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28300073/actin-binding-protein-coronin-1a-controls-osteoclastic-bone-resorption-by-regulating-lysosomal-secretion-of-cathepsin-k
#20
Saori Ohmae, Naruto Noma, Masayasu Toyomoto, Masahiro Shinohara, Masatoshi Takeiri, Hiroaki Fuji, Kenji Takemoto, Keiko Iwaisako, Tomoko Fujita, Norihiko Takeda, Makoto Kawatani, Mineyoshi Aoyama, Masatoshi Hagiwara, Yasushi Ishihama, Masataka Asagiri
Osteoclasts degrade bone matrix proteins via the secretion of lysosomal enzymes. However, the precise mechanisms by which lysosomal components are transported and fused to the bone-apposed plasma membrane, termed ruffled border membrane, remain elusive. Here, we identified coronin 1A as a negative regulator of exocytotic release of cathepsin K, one of the most important bone-degrading enzymes in osteoclasts. The modulation of coronin 1A expression did not alter osteoclast differentiation and extracellular acidification, but strongly affected the secretion of cathepsin K and osteoclast bone-resorption activity, suggesting the coronin 1A-mediated regulation of lysosomal trafficking and protease exocytosis...
March 16, 2017: Scientific Reports
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