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https://www.readbyqxmd.com/read/29911254/ubiquitin-regulation-of-trk-receptor-trafficking-and-degradation
#1
S S Murray, A W Wong, J Yang, Y Li, U Putz, S-S Tan, J Howitt
The regulation of Trk receptors is critical for orchestrating multiple signalling pathways required for developing and maintaining neuronal networks. Activation of Trk receptors results in signalling, internalisation and subsequent degradation of the protein. Although ubiquitination of TrkA by Nedd4-2 has been identified as an important degradation pathway, much less is known about the pathways regulating the degradation of TrkB and TrkC. Critical to the interaction between TrkA and Nedd4-2 is a PPxY motif present within TrkA but absent in TrkB and TrkC...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29907658/degradation-of-dendritic-cargos-requires-rab7-dependent-transport-to-somatic-lysosomes
#2
Chan Choo Yap, Laura Digilio, Lloyd P McMahon, A Denise R Garcia, Bettina Winckler
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D-positive lysosomes decreases steeply past the proximal segment...
June 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29891447/-changes-in-autophagy-during-maturation-and-differentiation-of-hepa1-6-cells-induced-by-all-trans-retinoic-acid
#3
Shu-Yu Fang, Jie-Jie Cui, Meng-Jia Gong, Yun He, Jing-Fang Zhang, Yang Bi
OBJECTIVE: To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells. MONTHOD: Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29807041/bombyx-mori-nucleopolyhedrovirus-utilizes-a-clathrin-and-dynamin-dependent-endocytosis-entry-pathway-into-bmn-cells
#4
Min Feng, Jianjia Zhang, Weifan Xu, Haiping Wang, Xiangshuo Kong, Xiaofeng Wu
Bombyx mori nucleopolyhedrovirus (BmNPV) is a leading cause of silkworm mortality and economic loss to sericulture. The entry of BmNPV budded virus (BV) into host cells is a fundamental process required for the initiation of infection. However, our understanding of the mechanism of virus entry is limited and it is unclear whether BV enter BmN cells via clathrin-mediated endocytosis. In this study, we found that BV enter BmN cells through a low-pH-dependent endocytosis pathway. Inhibition assays, transmission electron microscopy (TEM) analysis, and small interfering RNAs (siRNAs) knockdown assays revealed that BV entry into BmN cells is mediated by clathrin-dependent endocytosis...
May 25, 2018: Virus Research
https://www.readbyqxmd.com/read/29769350/rab5-rab7-and-rab11-are-required-for-caveolae-dependent-endocytosis-of-classic-swine-fever-virus-in-porcine-alveolar-macrophages
#5
Yun-Na Zhang, Ya-Yun Liu, Fu-Chuan Xiao, Chun-Chun Liu, Xiao-Dong Liang, Jing Chen, Jing Zhou, Abdul Sattar Baloch, Lin Kan, Bin Zhou, Hua-Ji Qiu
The members of Flaviviridae utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells). More importantly, the trafficking of CSFV within endosomes controlled by Rab GTPases is unknown in 3D4/21 cells. In this study, entry and post-internalization of CSFV were analyzed using chemical inhibitors, RNA interference, and dominant negative (DN) mutants...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29747217/fyco1-mediates-clearance-of-%C3%AE-synuclein-aggregates-through-a-rab7-dependent-mechanism
#6
Theodora Saridaki, Markus Nippold, Elisabeth Dinter, Andreas Roos, Leonie Diederichs, Luisa Fensky, Jörg B Schulz, Björn H Falkenburger
Parkinson disease can be caused by mutations in the α-synuclein gene and is characterized by aggregates of α-synuclein protein. We have previously shown that overexpression of the small GTPase Rab7 can induce clearance of α-synuclein aggregates. In this study, we investigate which Rab7 effectors mediate this effect. To model Parkinson disease we expressed the pathogenic A53T mutant of α-synuclein in HEK293T cells and Drosophila melanogaster. We tested the Rab7 effectors FYVE and coiled-coil domain-containing protein 1 (FYCO1) and Rab-interacting lysosomal protein (RILP)...
May 10, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29712939/essential-role-of-the-a3-isoform-of-v-atpase-in-secretory-lysosome-trafficking-via-rab7-recruitment
#7
Naomi Matsumoto, Mizuki Sekiya, Koujiro Tohyama, Eri Ishiyama-Matsuura, Ge-Hong Sun-Wada, Yoh Wada, Masamitsu Futai, Mayumi Nakanishi-Matsui
Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29668757/actin-polymerization-in-the-endosomal-pathway-but-not-on-the-coxiella-containing-vacuole-is-essential-for-pathogen-growth
#8
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 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
#9
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...
July 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29602783/quantitative-imaging-flow-cytometry-of-legionella-infected-dictyostelium-amoebae-reveals-the-impact-of-retrograde-trafficking-on-pathogen-vacuole-composition
#10
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 D...
June 1, 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
#11
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
#12
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
#13
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...
April 2, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29549340/transcytosis-of-trka-leads-to-diversification-of-dendritic-signaling-endosomes
#14
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
#15
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
#16
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 major histocompatibility complex class I (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 to CD4 and MHC-I. We confirm that Nef excludes Ser5 from human immunodeficiency virus type 1 (HIV-1) virions by downregulating its cell surface expression via similar functional motifs required for CD4 downregulation...
June 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29514857/rab7-knockout-unveils-regulated-autolysosome-maturation-induced-by-glutamine-starvation
#17
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 or 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 (herein referring to the Rab7a isoform) caused an accumulation of a massive number of LC3-positive autolysosomes under nutrient-rich conditions, indicating that Rab7 is dispensable for autophagosome-lysosome fusion...
April 6, 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
#18
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...
March 5, 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
#19
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...
March 6, 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
#20
Jieqiong Gao, Lars Langemeyer, Daniel Kümmel, 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
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