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https://www.readbyqxmd.com/read/28650718/subversion-of-rab5-regulated-autophagy-by-the-intracellular-pathogen-ehrlichia-chaffeensis
#1
Yasuko Rikihisa
Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate. Ehrlichia chaffeensis, an obligatory intracellular bacterium, resides in specialized membrane-bound inclusions that have early endosome-like characteristics, e.g., resident RAB5 GTPase and RAB5 effectors, including VPS34 (the catalytic subunit of class III phosphatidylinositol 3-kinase), but the inclusions lack late endosomal or lysosomal markers. Within inclusions, Ehrlichia obtains host-derived nutrients by inducing RAB5-regulated autophagy using Ehrlichia translocated factor-1 deployed by its type IV secretion system...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28648518/selective-inhibition-of-bet-proteins-reduces-pancreatic-damage-and-systemic-inflammation-in-bile-acid-and-fatty-acid-ethyl-ester-but-not-caerulein-induced-acute-pancreatitis-in-mice
#2
Wei Huang, Andrea C Haynes, Rajarshi Mukherjee, Li Wen, Diane Latawiec, Alexei V Tepikin, David N Criddle, Rab K Prinjha, Nicholas Smithers, Robert Sutton
OBJECTIVES: To evaluate the therapeutic potential of I-BET-762, an inhibitor of the bromodomain and extra-terminal (BET) protein family, in experimental acute pancreatitis (AP). METHODS: AP was induced in mice by retrograde infusion of taurolithocholic acid sulphate into the biliopancreatic duct (TLCS-AP) or two intraperitoneal (i.p.) injections of ethanol and palmitoleic acid 1 h apart (FAEE-AP) or 12 hourly i.p. injections of caerulein (CER-AP). In all treatment groups, I-BET-762 (30 mg/kg, i...
June 10, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28643160/residual-ground-water-levels-of-the-neonicotinoid-thiacloprid-perturb-chemosensing-of-caenorhabditis-elegans
#3
Hannah Hopewell, Kieran G Floyd, Daniel Burnell, John T Hancock, Joel Allainguillaume, Michael R Ladomery, Ian D Wilson
This study investigated the neurological effects of residual ground-water levels of thiacloprid on the non-target organism Caenorhabditis elegans. Nematodes treated with thiacloprid showed a dose-dependent and significantly increased twitch response at concentrations above 50 ng mL(-1) that disabled their forward locomotion in liquid culture. In comparison with untreated controls, 10 ng mL(-1) thiacloprid perturbed the chemosensory ability of C. elegans such that the nematodes no longer demonstrated positive chemotaxis towards a NaCl chemo-attractant, reducing their chemotaxis index from +0...
June 22, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28642685/rab-interacting-molecules-2-and-3-directly-interact-with-the-pore-forming-cav1-3-ca-2-channel-subunit-and-promote-its-membrane-expression
#4
Maria M Picher, Ana-Maria Oprişoreanu, SangYong Jung, Katrin Michel, Susanne Schoch, Tobias Moser
Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca(2+) channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca(2+) channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28637767/a-short-region-upstream-of-the-yeast-vacuolar-qa-snare-heptad-repeats-promotes-membrane-fusion-through-enhanced-snare-complex-assembly
#5
Hongki Song, William Wickner
While SNARE heptad-repeats are well studied, SNAREs also have upstream N-domains of indeterminate function. The assembly of yeast vacuolar SNAREs into complexes for fusion can be studied in chemically-defined reactions. Complementary proteoliposomes bearing a Rab:GTP and either the vacuolar R-SNARE or one of the 3 integrally-anchored Q-SNAREs were incubated with the tethering/SM protein complex HOPS and the two other soluble SNAREs (lacking a trans-membrane anchor) or their SNARE heptad-repeat domains. Fusion required a trans-membrane anchored R-SNARE on one membrane and an anchored Q-SNARE on the other...
June 21, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28636623/the-basolateral-vesicle-sorting-machinery-and-basolateral-proteins-are-recruited-to-the-site-of-enteropathogenic-e-coli-microcolony-growth-at-the-apical-membrane
#6
Gitte A Pedersen, Helene H Jensen, Anne-Sofie B Schelde, Charlotte Toft, Hans N Pedersen, Maj Ulrichsen, Frédéric H Login, Manuel R Amieva, Lene N Nejsum
Foodborne Enteropathogenic Escherichia coli (EPEC) infections of the small intestine cause diarrhea especially in children and are a major cause of childhood death in developing countries. EPEC infects the apical membrane of the epithelium of the small intestine by attaching, effacing the microvilli under the bacteria and then forming microcolonies on the cell surface. We first asked the question where on epithelial cells EPEC attaches and grows. Using models of polarized epithelial monolayers, we evaluated the sites of initial EPEC attachment to the apical membrane and found that EPEC preferentially attached over the cell-cell junctions and formed microcolonies preferentially where three cells come together at tricellular tight junctions...
2017: PloS One
https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#7
Waqas Ahmad, Yingying Li, Yidi Guo, Xinyu Wang, Ming Duan, Zhenhong Guan, Zengshan Liu, Maolin Zhang
Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated...
June 16, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#8
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#9
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632484/rab-gtpases-and-their-interacting-protein-partners-structural-insights-into-rab-functional-diversity
#10
Olena Pylypenko, Hussein Hammich, I-Mei Yu, Anne Houdusse
Rab molecular switches are key players in defining membrane identity and regulating intracellular trafficking events in eukaryotic cells. In spite of their global structural similarity, Rab-family members acquired particular features that allow them to perform specific cellular functions. The overall fold and local sequence conservations enable them to utilize a common machinery for prenylation and recycling; while individual Rab structural differences determine interactions with specific partners such as GEFs, GAPs and effector proteins...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28631105/stent-fracture-is-associated-with-a-higher-mortality-in-patients-with-type-2-diabetes-treated-by-implantation-of-a-second-generation-drug-eluting-stent
#11
Zhen Ge, Zhi-Zhong Liu, Jing Kan, Jun-Jie Zhang, Sui-Ji Li, Nai-Liang Tian, Fei Ye, Xue-Song Qian, Song Yang, Meng-Xuan Chen, Tanveer S Rab, Shao-Liang Chen
Type 2 diabetes correlates with clinical events after the implantation of a second-generation drug-eluting stent (DES). The rate and prognostic value of stent fracture (SF) in patients with diabetes who underwent DES implantation remain unknown. A total of 1160 patients with- and 2251 without- diabetes, who underwent surveillance angiography at 1 year after DES implantation between June 2004 and August 2014, were prospectively studied. The primary endpoints included the incidence of SF and a composite major adverse cardiac event [MACE, including myocardial infarction (MI), cardiac death, and target-vessel revascularization (TVR)] at 1-year follow-up and at the end of follow-up for overall patients, and target lesion failure [TLF, including cardiac death, target vessel myocardial infarction (TVMI) and target lesion revascularization (TLR)] at the end of study for SF patients...
June 19, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28628388/coordination-of-ampa-receptor-trafficking-by-rab-small-gtpases
#12
Angelika Hausser, Katalin Schlett
Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPA-type glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD)...
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28623606/marcks-is-necessary-for-oligodendrocyte-precursor-cell-maturation
#13
Zhao-Huan Zhang, Fan-Fei Ma, Hui Zhang, Xiao-Hui Xu
Oligodendrocyte precursor cell (OPC) development into myelinated oligodendrocytes demands vigorous membrane addition. Since myristoylated alanine-rich C-kinase substrate (MARCKS) reportedly contributes to Ras-associated protein (Rab)-10-associated vesicle insertion into neuronal membranes, we investigated the role of MARCKS in OPC maturation. We found that either knockdown of MARCKS or interruption of its interaction with Rab10 would cause a decrease of the cell membrane area during OPC development. Enhanced MARCKS phosphorylation by Nogo66 or myelin debris treatment inhibited OPC maturation, while its dephosphorylation by protein phosphatase 2 A activator D-erythro-sphingosine promoted OPC development in the presence of myelin debris...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28621911/different-roles-of-cd4-cd8-and-%C3%AE-%C3%AE-t-lymphocytes-in-naive-and-vaccinated-chickens-during-s-enteritidis-infection
#14
Zuzana Sekelova, Ondrej Polansky, Hana Stepanova, Radek Fedr, Marcela Faldynova, Ivan Rychlik, Lenka Vlasatikova
Lymphocytes represent the key antigen-specific leukocyte subpopulation. Despite their importance in mounting an immune response, an unbiased description of proteins expressed by chicken lymphocytes has not been presented. In this study we therefore intravenously infected chickens with Salmonella Enteritidis, sorted CD4, CD8 and γδ T-lymphocytes from the spleen by flow cytometry and determined the proteome of each population by LC-MS/MS. CD4 T-lymphocyte characteristic proteins included ubiquitin SUMO-like domain and BAR domain containing proteins...
June 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28619718/click-chemistry-enables-preclinical-evaluation-of-targeted-epigenetic-therapies
#15
Dean S Tyler, Johanna Vappiani, Tatiana Cañeque, Enid Y N Lam, Aoife Ward, Omer Gilan, Yih-Chih Chan, Antje Hienzsch, Anna Rutkowska, Thilo Werner, Anne J Wagner, Dave Lugo, Richard Gregory, Cesar Ramirez Molina, Neil Garton, Christopher R Wellaway, Susan Jackson, Laura MacPherson, Margarida Figueiredo, Sabine Stolzenburg, Charles C Bell, Colin House, Sarah-Jane Dawson, Edwin D Hawkins, Gerard Drewes, Rab K Prinjha, Raphaël Rodriguez, Paola Grandi, Mark A Dawson
The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. Here we modify BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click-chemistry and can be used as molecular probes in vitro and in vivo. Using click-proteomics and click-sequencing we explore the gene regulatory function of bromodomain containing 4 protein (BRD4) and the transcriptional changes induced by BET inhibitors. Studying mouse models of acute leukemia, we use high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments...
June 15, 2017: Science
https://www.readbyqxmd.com/read/28613117/heavy-subunit-of-cell-surface-gal-galnac-lectin-hgl-undergoes-degradation-via-endo-lysosomal-compartments-in-entamoeba-histolytica
#16
Kuldeep Verma, Sunando Datta
The human gut parasite Entamoeba histolytica uses a multifunctional virulence factor, Hgl, a cell surface transmembrane receptor subunit of Gal/GalNAc lectin that contributes to adhesion, invasion, cytotoxicity and immune response in the host. At present, the physiological importance of Hgl receptor is mostly known for pathogenicity of E. histolytica. However, the molecular mechanisms of Hgl trafficking events and their association with the intracellular membrane transport machinery are largely unknown. We employed biochemical and microscopy-based assays to understand the Hgl trafficking in the amoebic trophozoites...
June 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/28610953/a-thirty-year-quest-for-a-role-of-r-ras-in-cancer-from-an-oncogene-to-a-multitasking-gtpase
#17
Wai Nam Liu, Mingfei Yan, Andrew M Chan
Since the identification of R-Ras, which is the first Ras-related GTPase isolated based on sequence similarity to the classical RAS oncogene, more than 160 members of the Ras superfamily of GTPases have been identified and classified into the Ras, Rho, Rap, Rab, Ran, Arf, Rheb, RGK, Rad, Rit, and Miro subfamilies. R-Ras belongs to the Ras subfamily of small G-proteins, which are frequently implicated in cell growth and differentiation. Although the roles of R-Ras in cellular transformation and integrin-mediated cell adhesion have been extensively studied, the physiological function of this enigmatic G-protein was only revealed when a mouse strain deficient in R-Ras was generated...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28607399/rim1-2-in-retinal-ganglion-cells-are-required-for-the-refinement-of-ipsilateral-axons-and-eye-specific-segregation
#18
Ahlem Assali, Corentin Le Magueresse, Mohamed Bennis, Xavier Nicol, Patricia Gaspar, Alexandra Rebsam
Neural activity is crucial for the refinement of neuronal connections during development, but the contribution of synaptic release mechanisms is not known. In the mammalian retina, spontaneous neural activity controls the refinement of retinal projections to the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) to form appropriate topographic and eye-specific maps. To evaluate the role of synaptic release, the rab-interacting molecules (RIMs), a family of active zone proteins that play a central role in calcium-triggered release, were conditionally ablated in a subset of retinal ganglion cells (RGCs)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28604748/isoprenylcysteine-carboxylmethyltransferase-function-is-essential-for-rab4a-mediated-integrin-%C3%AE-3-recycling-cell-migration-and-cancer-metastasis
#19
M T Do, T F Chai, P J Casey, M Wang
Isoprenylcysteine carboxylmethyltransferase (ICMT) catalyzes the post-translational modification of RAB GTPases that contain C-terminal CXC motifs. However, the functional impact of this modification on RAB proteins has not been actively explored. We found that inhibition of ICMT significantly reduced cell migration in vitro and cancer invasion and metastasis in vivo. This role of ICMT was found to be mediated by RAB4A, an essential regulator of the fast recycling of integrin β3. Integrin β3 regulates cell polarity and migration when localized appropriately to the plasma membrane, thereby having an essential role in cancer metastasis...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28602209/update-on-glut4-vesicle-traffic-a-cornerstone-of-insulin-action
#20
REVIEW
Javier R Jaldin-Fincati, Martin Pavarotti, Scott Frendo-Cumbo, Philip J Bilan, Amira Klip
Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion...
June 8, 2017: Trends in Endocrinology and Metabolism: TEM
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