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https://www.readbyqxmd.com/read/29668757/actin-polymerization-in-the-endosomal-pathway-but-not-on-the-coxiella-containing-vacuole-is-essential-for-pathogen-growth
#1
Heather E Miller, Charles L Larson, Robert A Heinzen
Coxiella burnetii is an intracellular bacterium that replicates within an expansive phagolysosome-like vacuole. Fusion between the Coxiella-containing vacuole (CCV) and late endosomes/multivesicular bodies requires Rab7, the HOPS tethering complex, and SNARE proteins, with actin also speculated to play a role. Here, we investigated the importance of actin in CCV fusion. Filamentous actin patches formed around the CCV membrane that were preferred sites of vesicular fusion. Accordingly, the mediators of endolysosomal fusion Rab7, VAMP7, and syntaxin 8 were concentrated in CCV actin patches...
April 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29656126/epigallocatechin-3-gallate-protects-kuruma-shrimp-marsupeneaus-japonicus-from-white-spot-syndrome-virus-and-vibrio-alginolyticus
#2
Zhi Wang, Baozhen Sun, Fei Zhu
Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and exhibits potential antibacterial and anticancer activities. In this study, EGCG was used in pathogen-challenge experiments in shrimp to discover its effect on the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus was used as an experimental model and challenged with white spot syndrome virus (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge experiments showed that EGCG pretreatment significantly delayed and reduced mortality upon WSSV and V...
April 12, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29602783/quantitative-imaging-flow-cytometry-of-legionella-infected-dictyostelium-reveals-the-impact-of-retrograde-trafficking-on-pathogen-vacuole-composition
#3
Amanda Welin, Stephen Weber, Hubert Hilbi
The ubiquitous environmental bacterium Legionella pneumophila survives and replicates within amoebae and human macrophages by forming a Legionella -containing vacuole (LCV). In an intricate process governed by the bacterial Icm/Dot type IV secretion system and a plethora of "effector proteins" the nascent LCV interferes with a number of intracellular trafficking pathways, including retrograde transport from endosomes to the Golgi apparatus. Conserved retrograde trafficking components such as the retromer coat complex or the phosphoinositide (PI) 5-phosphatase Dd5P4/OCRL restrict intracellular replication of L...
March 30, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29599388/correction-for-toyofuku-et-al-leucine-rich-repeat-kinase-1-regulates-autophagy-through-turning-on-tbc1d2-dependent-rab7-inactivation
#4
Toshihiko Toyofuku, Keiko Morimoto, Shigemi Sasawatari, Atsusi Kumanogoh
No abstract text is available yet for this article.
April 15, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29551770/%C3%AE-catenin-knockdown-promotes-nherf1-mediated-survival-of-colorectal-cancer-cells-implications-for-a-double-targeted-therapy
#5
Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Giuseppe La Regina, Luca Mologni, Valeria Famiglini, Valentina Naccarato, Daniela Bonetti, Candice Gautier, Stefano Gianni, Daniele Vergara, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Romano Silvestri, Carlo Gambacorti Passerini, Michele Maffia, Addolorata Maria Luce Coluccia
Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+ /H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity...
March 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29551411/live-observation-of-two-parallel-membrane-degradation-pathways-at-axon-terminals
#6
Eugene Jennifer Jin, Ferdi Ridvan Kiral, Mehmet Neset Ozel, Lara Sophie Burchardt, Marc Osterland, Daniel Epstein, Heike Wolfenberg, Steffen Prohaska, Peter Robin Hiesinger
Neurons are highly polarized cells that require continuous turnover of membrane proteins at axon terminals to develop, function, and survive. Yet, it is still unclear whether membrane protein degradation requires transport back to the cell body or whether degradation also occurs locally at the axon terminal, where live observation of sorting and degradation has remained a challenge. Here, we report direct observation of two cargo-specific membrane protein degradation mechanisms at axon terminals based on a live-imaging approach in intact Drosophila brains...
March 3, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29549340/transcytosis-of-trka-leads-to-diversification-of-dendritic-signaling-endosomes
#7
Kelly Barford, Austin Keeler, Lloyd McMahon, Kathryn McDaniel, Chan Choo Yap, Christopher D Deppmann, Bettina Winckler
The development of the peripheral nervous system relies on long-distance signaling from target organs back to the soma. In sympathetic neurons, this long-distance signaling is mediated by target derived Nerve Growth Factor (NGF) interacting with its axonal receptor, TrkA. This ligand receptor complex internalizes into what is commonly referred to as the signaling endosome which is transported retrogradely to the soma and dendrites to mediate survival signaling and synapse formation, respectively. The molecular identity of signaling endosomes in dendrites has not yet been determined...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29545877/3-methyladenine-and-dexmedetomidine-reverse-lipopolysaccharide-induced-acute-lung-injury-through-the-inhibition-of-inflammation-and-autophagy
#8
Dengfeng Ding, Shiyuan Xu, Hongfei Zhang, Wei Zhao, Xueping Zhang, Yuanxu Jiang, Ping Wang, Zhongliang Dai, Junzhi Zhang
The aim of the present study was to investigate the effects of 3-methyladenine (3-MA) and dexmedetomidine (DEX) pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism underlying the effects. LPS was instilled into the trachea of BALB/c mice to induce the ALI model. Solutions of 3-MA or DEX were intravenously injected into the mice 1 h later to establish the 3-MA and DEX groups. On days 1, 3 and 5 after the injections, arterial blood gas analysis was conducted, and the lung wet-dry weight ratio (W/D) was determined...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29514909/hiv-1-nef-antagonizes-serinc5-restriction-by-downregulation-of-serinc5-via-the-endosome-lysosome-system
#9
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29514857/rab7-knockout-unveiled-regulated-autolysosome-maturation-induced-by-glutamine-starvation
#10
Yoshihiko Kuchitsu, Yuta Homma, Naonobu Fujita, Mitsunori Fukuda
Macroautophagy (simply called autophagy hereafter) is an intracellular degradation mechanism that is activated by nutrient starvation. Although it is well-known that starvation induces autophagosome formation in an mTORC1-dependent manner, whether starvation also regulates autophagosome/autolysosome maturation was unclear. In the present study we succeeded in demonstrating that starvation activates autolysosome maturation in mammalian cells. We found that knockout (KO) of Rab7 caused accumulation of a massive number of LC3-positive autolysosomes under nutrient-rich conditions, indicating that Rab7 is dispensable for autophagosome-lysosome fusion...
March 7, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29478853/remodeling-the-specificity-of-an-endosomal-corvet-tether-underlies-formation-of-regulated-secretory-vesicles-in-the-ciliate-tetrahymena-thermophila
#11
Daniela Sparvoli, Elisabeth Richardson, Hiroko Osakada, Xun Lan, Masaaki Iwamoto, Grant R Bowman, Cassandra Kontur, William A Bourland, Denis H Lynn, Jonathan K Pritchard, Tokuko Haraguchi, Joel B Dacks, Aaron P Turkewitz
In the endocytic pathway of animals, two related complexes, called CORVET (class C core vacuole/endosome transport) and HOPS (homotypic fusion and protein sorting), act as both tethers and fusion factors for early and late endosomes, respectively. Mutations in CORVET or HOPS lead to trafficking defects and contribute to human disease, including immune dysfunction. HOPS and CORVET are conserved throughout eukaryotes, but remarkably, in the ciliate Tetrahymena thermophila, the HOPS-specific subunits are absent, while CORVET-specific subunits have proliferated...
February 21, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29463724/distinct-sets-of-tethering-complexes-snare-complexes-and-rab-gtpases-mediate-membrane-fusion-at-the-vacuole-in-arabidopsis
#12
Kodai Takemoto, Kazuo Ebine, Jana Christin Askani, Falco Krüger, Zaida Andrés Gonzalez, Emi Ito, Tatsuaki Goh, Karin Schumacher, Akihiko Nakano, Takashi Ueda
Membrane trafficking plays pivotal roles in various cellular activities and higher-order functions of eukaryotes and requires tethering factors to mediate contact between transport intermediates and target membranes. Two evolutionarily conserved tethering complexes, homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET), are known to act in endosomal/vacuolar transport in yeast and animals. Both complexes share a core subcomplex consisting of Vps11, Vps18, Vps16, and Vps33, and in addition to this core, HOPS contains Vps39 and Vps41, whereas CORVET contains Vps3 and Vps8...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29446751/molecular-mechanism-to-target-the-endosomal-mon1-ccz1-gef-complex-to-the-pre-autophagosomal-structure
#13
Jieqiong Gao, Lars Langemeyer, Daniel Kuemmel, Fulvio Reggiori, Christian Ungermann
During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family...
February 15, 2018: ELife
https://www.readbyqxmd.com/read/29425100/the-rab-effector-protein-rabep2-regulates-endosomal-trafficking-to-mediate-vascular-endothelial-growth-factor-receptor-2-vegfr2-dependent-signaling
#14
Natalie Kofler, Federico Corti, Felix Rivera-Molina, Yong Deng, Derek Toomre, Michael Simons
As a master regulator of endothelial cell function, vascular endothelial growth factor receptor-2 (VEGFR2) activates multiple downstream signaling pathways that are critical for vascular development and normal vessel function. VEGFR2 trafficking through various endosomal compartments modulates its signaling output. Accordingly, proteins that regulate the speed and direction by which VEGFR2 traffics through endosomes have been demonstrated to be particularly important for arteriogenesis. However, little is known about how these proteins control VEGFR2 trafficking and about the implications of this control for endothelial cell function...
February 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29408503/common-traffic-routes-for-imported-spermine-and-endosomal-glypican-1-derived-heparan-sulfate-in-fibroblasts
#15
Fang Cheng, Lars-Åke Fransson, Katrin Mani
Import of the polyamine spermine from the extracellular environment depends on the presence of cell surface heparan sulfate proteoglycans, such as glypican-1. This proteoglycan is internalized by endocytosis, releases its heparan sulfate chains in endosomes by a nitric oxide-, copper- and amyloid precursor protein-dependent mechanism, then penetrates the membrane and is transported to the nucleus and then to autophagosomes. This process is spontaneous or induced by ascorbate depending on the growth-state of the cell...
February 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29404450/ethanol-exposure-inhibits-hepatocyte-lipophagy-by-inactivating-the-small-guanosine-triphosphatase-rab7
#16
Ryan J Schulze, Karuna Rasineni, Shaun G Weller, Micah B Schott, Barbara Schroeder, Carol A Casey, Mark A McNiven
Alcohol consumption is a well-established risk factor for the onset and progression of fatty liver disease. An estimated 90% of heavy drinkers are thought to develop significant liver steatosis. For these reasons, an increased understanding of the molecular basis for alcohol-induced hepatic steatosis is important. It has become clear that autophagy, a catabolic process of intracellular degradation and recycling, plays a key role in hepatic lipid metabolism. We have shown that Rab7, a small guanosine triphosphatase known to regulate membrane trafficking, acts as a key orchestrator of hepatocellular lipophagy, a selective form of autophagy in which lipid droplets (LDs) are specifically targeted for turnover by the autophagic machinery...
April 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29382080/structural-studies-of-predicted-ligand-binding-sites-and-molecular-docking-analysis-of-slc2a4-as-a-therapeutic-target-for-the-treatment-of-cancer
#17
Raphael Taiwo Aruleba, Tayo Alex Adekiya, Babatunji Emmanuel Oyinloye, Abidemi Paul Kappo
Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer...
January 28, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29364868/mitochondria-lysosome-contacts-regulate-mitochondrial-fission-via-rab7-gtp-hydrolysis
#18
Yvette C Wong, Daniel Ysselstein, Dimitri Krainc
Both mitochondria and lysosomes are essential for maintaining cellular homeostasis, and dysfunction of both organelles has been observed in multiple diseases. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network, which drives cellular metabolism. Lysosomes similarly undergo constant dynamic regulation by the RAB7 GTPase, which cycles from an active GTP-bound state into an inactive GDP-bound state upon GTP hydrolysis. Here we have identified the formation and regulation of mitochondria-lysosome membrane contact sites using electron microscopy, structured illumination microscopy and high spatial and temporal resolution confocal live cell imaging...
February 15, 2018: Nature
https://www.readbyqxmd.com/read/29355788/the-kinetics-of-autophagy-in-the-lung-following-acute-spinal-cord-injury-in-rats
#19
Ruiliang Chu, Jiuling Wang, Yang Bi, Guoxin Nan
BACKGROUND CONTEXT: Lung injury is a major cause of respiratory complications following an acute spinal cord injury (ASCI), which are associated with a high mortality rate. Autophagy has been shown to be involved in a variety of lung diseases; however, whether autophagy is activated in the lung following ASCI remains unknown. PURPOSE: The objective of this study was to investigate the induction of autophagy in the lung after ASCI. STUDY DESIGN: This is an experimental animal study of ASCI investigating kinetics of autophagy in the lung following ASCI...
January 31, 2018: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/29336362/screening-for-sh3tc2-pmp2-and-bscl2-variants-in-a-cohort-of-chinese-patients-with-charcot-marie-tooth
#20
Xin Zhao, Ming-Ming Jiang, Yi-Zhou Yan, Lei Liu, Yong-Zhi Xie, Xiao-Bo Li, Zheng-Mao Hu, Xiao-Hong Zi, Kun Xia, Bei-Sha Tang, Ru-Xu Zhang
BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital...
January 20, 2018: Chinese Medical Journal
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