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https://www.readbyqxmd.com/read/28103630/orientia-tsutsugamushi-ank9-is-a-multifunctional-effector-that-utilizes-a-novel-grip-like-golgi-localization-domain-for-golgi-to-endoplasmic-reticulum-trafficking-and-interacts-with-host-copb2
#1
Andrea R Beyer, Kyle G Rodino, Lauren VieBrock, Ryan S Green, Brittney K Tegels, Lee D Oliver, Richard T Marconi, Jason A Carlyon
Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that afflicts one million people annually. This obligate intracellular bacterium boasts one of the largest microbial arsenals of ankyrin repeat-containing protein (Ank) effectors, most of which target the endoplasmic reticulum (ER) by undefined mechanisms. Ank9 is the only one proven to function during infection. Here, we demonstrate that Ank9 bears a motif that mimics the GRIP domain of eukaryotic golgins and is necessary and sufficient for its Golgi localization...
January 19, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28103577/association-of-rab5-overexpression-in-pancreatic-cancer-with-cancer-progression-and-poor-prognosis-via-e-cadherin-suppression
#2
Takamichi Igarashi, Kenichiro Araki, Takehiko Yokobori, Bolag Altan, Takahiro Yamanaka, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Norio Kubo, Tadashi Handa, Yasuo Hosouchi, Masahiko Nishiyama, Tetsunari Oyama, Ken Shirabe, Hiroyuki Kuwano
Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103481/motor-learning-requires-purkinje-cell-synaptic-potentiation-through-activation-of-ampa-receptor-subunit-glua3
#3
Nicolas Gutierrez-Castellanos, Carla M Da Silva-Matos, Kuikui Zhou, Cathrin B Canto, Maria C Renner, Linda M C Koene, Ozgecan Ozyildirim, Rolf Sprengel, Helmut W Kessels, Chris I De Zeeuw
Accumulating evidence indicates that cerebellar long-term potentiation (LTP) is necessary for procedural learning. However, little is known about its underlying molecular mechanisms. Whereas AMPA receptor (AMPAR) subunit rules for synaptic plasticity have been extensively studied in relation to declarative learning, it is unclear whether these rules apply to cerebellum-dependent motor learning. Here we show that LTP at the parallel-fiber-to-Purkinje-cell synapse and adaptation of the vestibulo-ocular reflex depend not on GluA1- but on GluA3-containing AMPARs...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28103137/cap-gly-proteins-contribute-to-microtubule-dependent-trafficking-via-interactions-with-the-c-terminal-aromatic-residue-of-%C3%AE-tubulin
#4
Annie Andrieux, Laurence Aubry, Cécile Boscheron
In mammals, the C-terminal tyrosine residue of α-tubulin is subjected to removal/re-addition cycles resulting in tyrosinated microtubules and detyrosinated Glu-microtubules. CLIP170 and its yeast ortholog (Bik1) interact weakly with Glu-microtubules. Recently, we described a Microtubule- Rho1- and Bik1-dependent mechanism involved in Snc1 routing. Here, we further show a contribution of the yeast p150Glued ortholog (Nip100) in Snc1 trafficking. Both CLIP170 and p150Glued are CAP-Gly-containing proteins that belong to the microtubule +end-tracking protein family (known as +Tips)...
January 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28102838/autophagy-dysregulation-in-danon-disease
#5
Anna Chiara Nascimbeni, Marina Fanin, Corrado Angelini, Marco Sandri
The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102201/direct-pip2-binding-mediates-stable-oligomer-formation-of-the-serotonin-transporter
#6
Andreas Anderluh, Tina Hofmaier, Enrico Klotzsch, Oliver Kudlacek, Thomas Stockner, Harald H Sitte, Gerhard J Schütz
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#7
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#8
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100664/rab1-interacts-with-golph3-and-controls-golgi-structure-and-contractile-ring-constriction-during-cytokinesis-in-drosophila-melanogaster
#9
Stefano Sechi, Anna Frappaolo, Roberta Fraschini, Luisa Capalbo, Marco Gottardo, Giorgio Belloni, David M Glover, Alan Wainman, Maria Grazia Giansanti
Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28100490/amino-terminal-domains-of-kainate-receptors-determine-the-differential-dependence-on-neto-auxiliary-subunits-for-trafficking
#10
Nengyin Sheng, Yun Stone Shi, Roger A Nicoll
The kainate receptor (KAR), a subtype of glutamate receptor, mediates excitatory synaptic responses at a subset of glutamatergic synapses. However, the molecular mechanisms underlying the trafficking of its different subunits are poorly understood. Here we use the CA1 hippocampal pyramidal cell, which lacks KAR-mediated synaptic currents, as a null background to determine the minimal requirements for the extrasynaptic and synaptic expression of the GluK2 subunit. We find that the GluK2 receptor itself, in contrast to GluK1, traffics to the neuronal surface and synapse efficiently and the auxiliary subunits Neto1 and Neto2 caused no further enhancement of these two trafficking processes...
January 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28100451/an-aphid-effector-targets-trafficking-protein-vps52-in-a-host-specific-manner-to-promote-virulence
#11
Patricia Rodriguez, Carmen Escudero-Martinez, Jorunn Bos
Plant- and animal-feeding insects secrete saliva inside their hosts, containing effectors, which may promote nutrient release and suppress immunity. Although for plant pathogenic microbes it is well established that effectors target host proteins to modulate host cell processes and promote disease, the host cell targets of herbivorous insects remain elusive. Here, we show that the existing plant pathogenic microbe effector paradigm can be extended to herbivorous insects in that effector-target interactions inside host cells modify critical host processes to promote plant susceptibility...
January 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28100109/stem-cell-trafficking-during-endometriosis
#12
Antonio Simone Laganà, Francesca Maria Salmeri, Salvatore Giovanni Vitale, Onofrio Triolo, Martin Götte
No abstract text is available yet for this article.
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28098827/shared-sulfur-mobilization-routes-for-trna-thiolation-and-molybdenum-cofactor-biosynthesis-in-prokaryotes-and-eukaryotes
#13
REVIEW
Silke Leimkühler, Martin Bühning, Lena Beilschmidt
Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm⁵s²U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure...
January 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28098786/retinoic-acid-and-its-role-in-modulating-intestinal-innate-immunity
#14
REVIEW
Paulo Czarnewski, Srustidhar Das, Sara M Parigi, Eduardo J Villablanca
Vitamin A (VA) is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans retinoic acid (atRA) has been shown to be crucial in inducing gut tropism in lymphocytes and modulating T helper differentiation. In addition to the widely recognized role in adaptive immunity, increasing evidence identifies atRA as an important modulator of innate immune cells, such as tolerogenic dendritic cells (DCs) and innate lymphoid cells (ILCs)...
January 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28098232/crystal-structure-of-sec10-a-subunit-of-the-exocyst-complex
#15
Jianxing Chen, Atsushi Yamagata, Keiko Kubota, Yusuke Sato, Sakurako Goto-Ito, Shuya Fukai
The exocyst complex is a heterooctameric protein complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84. This complex plays an essential role in trafficking secretory vesicles to the plasma membrane through its interaction with phosphatidylinositol 4,5-bisphosphate and small GTPases. To date, the near-full-length structural information of each subunit has been limited to Exo70, although the C-terminal half structures of Sec6, Sec15 and Exo84 and the structures of the small GTPase-binding domains of Sec3, Sec5 and Exo84 have been reported...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#16
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#17
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#18
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096376/myosin-driven-transport-network-in-plants
#19
Elizabeth G Kurth, Valera V Peremyslov, Hannah L Turner, Kira S Makarova, Jaime Iranzo, Sergei L Mekhedov, Eugene V Koonin, Valerian V Dolja
We investigate the myosin XI-driven transport network in Arabidopsis using protein-protein interaction, subcellular localization, gene knockout, and bioinformatics analyses. The two major groups of nodes in this network are myosins XI and their membrane-anchored receptors (MyoB) that, together, drive endomembrane trafficking and cytoplasmic streaming in the plant cells. The network shows high node connectivity and is dominated by generalists, with a smaller fraction of more specialized myosins and receptors...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096354/loss-of-get-pathway-orthologs-in-arabidopsis-thaliana-causes-root-hair-growth-defects-and-affects-snare-abundance
#20
Shuping Xing, Dietmar Gerald Mehlhorn, Niklas Wallmeroth, Lisa Yasmin Asseck, Ritwika Kar, Alessa Voss, Philipp Denninger, Vanessa Aphaia Fiona Schmidt, Markus Schwarzländer, York-Dieter Stierhof, Guido Grossmann, Christopher Grefen
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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