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https://www.readbyqxmd.com/read/29138318/snare-priming-is-essential-for-maturation-of-autophagosomes-but-not-for-their-formation
#1
Adi Abada, Smadar Levin-Zaidman, Ziv Porat, Tali Dadosh, Zvulun Elazar
Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by SNARE molecules have been postulated to promote autophagy. αSNAP, the adaptor molecule for the SNARE-priming enzyme N-ethylmaleimide-sensitive factor (NSF) is known to be crucial for intracellular membrane fusion processes, but its role in autophagy remains unclear...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29134198/%C3%AF-3-polyunsaturated-fatty-acids-direct-differentiation-of-the-membrane-phenotype-in-mesenchymal-stem-cells-to-potentiate-osteogenesis
#2
Kandice R Levental, Michal A Surma, Allison D Skinkle, Joseph H Lorent, Yong Zhou, Christian Klose, Jeffrey T Chang, John F Hancock, Ilya Levental
Mammalian cells produce hundreds of dynamically regulated lipid species that are actively turned over and trafficked to produce functional membranes. These lipid repertoires are susceptible to perturbations from dietary sources, with potentially profound physiological consequences. However, neither the lipid repertoires of various cellular membranes, their modulation by dietary fats, nor their effects on cellular phenotypes have been widely explored. We report that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts or adipocytes results in extensive remodeling of the plasma membrane (PM), producing cell-specific membrane compositions and biophysical properties...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29133912/the-multiple-antibiotic-resistance-operon-of-enteric-bacteria-controls-dna-repair-and-outer-membrane-integrity
#3
Prateek Sharma, James R J Haycocks, Alistair D Middlemiss, Rachel A Kettles, Laura E Sellars, Vito Ricci, Laura J V Piddock, David C Grainger
The multiple antibiotic resistance (mar) operon of Escherichia coli is a paradigm for chromosomally encoded antibiotic resistance in enteric bacteria. The locus is recognised for its ability to modulate efflux pump and porin expression via two encoded transcription factors, MarR and MarA. Here we map binding of these regulators across the E. coli genome and identify an extensive mar regulon. Most notably, MarA activates expression of genes required for DNA repair and lipid trafficking. Consequently, the mar locus reduces quinolone-induced DNA damage and the ability of tetracyclines to traverse the outer membrane...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133483/ctage5-deletion-in-pancreatic-%C3%AE-cells-impairs-proinsulin-trafficking-and-insulin-biogenesis-in-mice
#4
Junwan Fan, Yaqing Wang, Liang Liu, Hongsheng Zhang, Feng Zhang, Lei Shi, Mei Yu, Fei Gao, Zhiheng Xu
Proinsulin is synthesized in the endoplasmic reticulum (ER) in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. Defects in insulin biogenesis may cause diabetes. However, the underlying mechanisms for proinsulin transport are still not fully understood. We show that β cell-specific deletion of cTAGE5, also known as Mea6, leads to increased ER stress, reduced insulin biogenesis in the pancreas, and severe glucose intolerance in mice. We reveal that cTAGE5/MEA6 interacts with vesicle membrane soluble N-ethyl-maleimide sensitive factor attachment protein receptor Sec22b...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#5
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29132390/a-transwell-assay-that-excludes-exosomes-for-assessment-of-tunneling-nanotube-mediated-intercellular-communication
#6
Venugopal Thayanithy, Patrick O'Hare, Phillip Wong, Xianda Zhao, Clifford J Steer, Subbaya Subramanian, Emil Lou
BACKGROUND: Tunneling nanotubes (TNTs) are naturally-occurring filamentous actin-based membranous extensions that form across a wide spectrum of mammalian cell types to facilitate long-range intercellular communication. Valid assays are needed to accurately assess the downstream effects of TNT-mediated transfer of cellular signals in vitro. We recently reported a modified transwell assay system designed to test the effects of intercellular transfer of a therapeutic oncolytic virus, and viral-activated drugs, between cells via TNTs...
November 13, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29130391/the-vici-syndrome-protein-epg5-regulates-intracellular-nucleic-acid-trafficking-linking-autophagy-to-innate-and-adaptive-immunity
#7
E Piano Mortari, V Folgiero, V Marcellini, P Romania, E Bellacchio, V D'Alicandro, C Bocci, R Carrozzo, D Martinelli, S Petrini, E Axiotis, C Farroni, F Locatelli, U Schara, D Pilz, H Jungbluth, C Dionisi-Vici, R Carsetti
Vici syndrome is a human inherited multi-system disorder caused by recessive mutations in EPG5, encoding the EPG5 protein that mediates the fusion of autophagosomes with lysosomes. Immunodeficiency characterized by lack of memory B cells and increased susceptibility to infection is an integral part of the condition, but the role of EPG5 in the immune system remains unknown. Here we show that EPG5 is indispensable for the transport of the TLR9 ligand CpG to the late endosomal-lysosomal compartment, and for TLR9-initiated signaling, a step essential for the survival of human memory B cells and their ultimate differentiation into plasma cells...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29129703/identification-of-novel-mitochondrial-localization-signals-in-human-tafazzin-the-cause-of-the-inherited-cardiomyopathic-disorder-barth-syndrome
#8
Ana A Dinca, Wei-Ming Chien, Michael T Chin
Mutations in the gene tafazzin (TAZ) result in Barth syndrome (BTHS). Patients present with hypotonia, cyclic neutropenia, 3-methyglutaconic aciduria, and cardiomyopathy, which is the major cause of mortality. The recessive, X-linked TAZ gene encodes a mitochondrial membrane-associated phospholipid modifying enzyme, which adds unsaturated fatty acid species to monolysocardiolipin to generate mature cardiolipin in the mitochondrial membrane that is essential for mitochondrial morphology and function. To identify intrinsic mitochondrial localization sequences in the human TAZ protein, we made sequential TAZ peptide-eGFP fusion protein expression constructs and analyzed the localization of eGFP fluorescence by confocal microscopy...
November 9, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29129605/evolution-and-adaptation-of-single-pass-transmembrane-proteins
#9
Irina D Pogozheva, Andrei L Lomize
A comparative analysis of 6,039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication...
November 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29129580/the-%C3%AE-and-%C3%AE-2%C3%AE-auxiliary-subunits-of-cav1-channels-are-required-for-th2-lymphocyte-function-and-acute-allergic-airway-inflammation
#10
Nicolas Rosa, Emily Triffaux, Virginie Robert, Marion Mars, Martin Klein, Gregory Bouchaud, Astrid Canivet, Antoine Magnan, Jean-Charles Guéry, Lucette Pelletier, Magali Savignac
BACKGROUND: T-lymphocytes express not only the cell membrane calcium ORAI1 but also voltage-dependent Cav1 channels. In excitable cells, these channels are composed of the ion forming pore α1 and auxiliary subunits (β and α2δ) needed for proper trafficking and activation of the channel. We previously disclosed the role of Cav1.2 α1 in mouse and human Th2- but not Th1-cell functions and showed that knocking-down Cav1 α1 prevents experimental asthma OBJECTIVE: We investigated the role of β and α2δ auxiliary subunits on Cav1 α1 function in Th2 lymphocytes and on the development of acute allergic airway inflammation...
November 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29128397/identification-and-characterization-of-molluscan-caveolin-1-ortholog-from-haliotis-discus-discus-possible-involvement-in-embryogenesis-and-host-defense-mechanism-against-pathogenic-stress
#11
H M V Udayantha, S D N K Bathige, Thanthrige Thiunuwan Priyathilaka, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Caveolins are principal membrane proteins of caveolae that play a central role in signal transduction, substrate transport, and membrane trafficking in various cell types. Numerous studies have reported the crucial role of caveolin-1 (CAV1) in response to invading microbes; yet, very little is known about molluscan CAV1. In this study, we identified and characterized CAV1 ortholog from the disk abalone, Haliotis discus discus (HdCAV1). The cDNA sequence of HdCAV1 is 826 bp long and encodes a 127-amino acid polypeptide...
November 8, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29125865/membrane-order-in-the-plasma-membrane-and-endocytic-recycling-compartment
#12
David B Iaea, Frederick R Maxfield
The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment...
2017: PloS One
https://www.readbyqxmd.com/read/29123973/cholera-toxin-b-subunit-induces-local-curvature-on-lipid-bilayers
#13
Weria Pezeshkian, Lina J Nåbo, John H Ipsen
The B subunit of the bacterial cholera toxin (CTxB) is responsible for the toxin binding to the cell membrane and its intracellular trafficking. CTxB binds to the monosialotetrahexosyl ganglioside at the plasma membrane of the target cell and mediates toxin internalization by endocytosis. CTxB induces a local membrane curvature that is essential for its clathrin-independent uptake. Using all-atom molecular dynamics, we show that CTxB induces local curvature, with the radius of curvature around 36 nm. The main feature of the CTxB molecular structure that causes membrane bending is the protruding alpha helices in the middle of the protein...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29123471/vglut2-trafficking-is-differentially-regulated-by-adaptor-proteins-ap-1-and-ap-3
#14
Haiyan Li, Magda S Santos, Chihyung K Park, Yuriy Dobry, Susan M Voglmaier
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#15
REVIEW
Jocelyn Widagdo, Sumasri Guntupalli, Se E Jang, Victor Anggono
The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs) is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29122514/chlamydia-trachomatis-and-its-interaction-with-the-cellular-retromer
#16
REVIEW
Sebastian Banhart, Laura Rose, Lukas Aeberhard, Sophia Koch-Edelmann, Dagmar Heuer
Chlamydia trachomatis is an important human pathogen. This obligate intracellular bacterium grows inside the eukaryotic cell in a membrane-bound compartment, the inclusion. Recent global approaches describe the interactions of C. trachomatis with its host cell and indicate the inclusion is an intracellular trafficking hub embedded into the cellular vesicular trafficking pathways recruiting subunits of the retromer protein complex of the host cell. Here we review these recent developments in deciphering Chlamydia-host cell interactions with emphasis on the role of the retromer complex...
October 26, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29121260/an-arf-gap-promotes-endocytosis-and-hyphal-growth-of-ashbya-gossypii
#17
Therese Oscarsson, Andrea Walther, Klaus B Lengeler, Jürgen Wendland
The ADP-ribosylation factor (ARF) family of GTPases are highly conserved from yeast to human and regulate vesicle budding. Sec7 domain containing proteins stimulate the guanine nucleotide exchange on Arf proteins while ARF-GTPase activating proteins stimulate the hydrolysis of GTP. Since vesicle trafficking is important for hyphal growth we studied the A. gossypii homolog of S. cerevisiae ARF3 along with its putative GEF and GAP encoded by YEL1 and GTS1, respectively. Deletion of YEL1 had no discernible phenotype and deletion of ARF3 had only a minor defect in vacuolar fusion...
November 7, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29118375/the-lipid-raft-dwelling-protein-us9-can-be-manipulated-to-target-app-compartmentalization-app-processing-and-neurodegenerative-disease-pathogenesis
#18
Renato Brandimarti, Gordon S Hill, Jonathan D Geiger, Olimpia Meucci
The trafficking behavior of the lipid raft-dwelling US9 protein from Herpes Simplex Virus strikingly overlaps with that of the amyloid precursor protein (APP). Both US9 and APP processing machinery rely on their ability to shuttle between endosomes and plasma membranes, as well as on their lateral accumulation in lipid rafts. Therefore, repurposing US9 to track/modify these molecular events represents a valid approach to investigate pathological states including Alzheimer's disease and HIV-associated neurocognitive disorders where APP misprocessing to amyloid beta formation has been observed...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117938/functional-characterization-of-avpr2-mutants-found-in-turkish-patients-with-nephrogenic-diabetes-insipidus
#19
Beril Erdem, Angela Schulz, Emel Saglar, Ferhat Deniz, Torsten Schoneberg, Hatice Mergen
Diabetes insipidus is a rare disorder characterized by an impairment in water balance because of the inability to concentrate urine. While central Diabetes insipidus is caused by mutations in the AVP, the reason for genetically determined nephrogenic Diabetes insipidus can be mutations in AQP2 or AVPR2. After release of AVP from posterior pituitary into blood stream it binds to AVPR2 which is one of the receptors for AVP and is mainly expressed in principal cells of collecting ducts of kidney. Receptor activation increases cAMP levels in principal cells, resulting in the incorporation of AQP2 into the membrane, finally increasing water reabsorption...
November 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29117568/pten-regulates-glucose-transporter-recycling-by-impairing-snx27-retromer-assembly
#20
Swapnil Rohidas Shinde, Subbareddy Maddika
The tumor suppressor PTEN executes cellular functions predominantly through its phosphatase activity. Here we identified a phosphatase-independent role for PTEN during vesicular trafficking of the glucose transporter GLUT1. PTEN physically interacts with SNX27, a component of the retromer complex that recycles transmembrane receptors such as GLUT1 from endosomes to the plasma membrane. PTEN binding with SNX27 prevents GLUT1 accumulation at the plasma membrane because of defective recycling and thus reduces cellular glucose uptake...
November 7, 2017: Cell Reports
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