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https://www.readbyqxmd.com/read/29774516/periodic-variation-of-aak1-in-an-a%C3%AE-1-42-induced-mouse-model-of-alzheimer-s-disease
#1
Xue Fu, Meiling Ke, Weihua Yu, Xia Wang, Qian Xiao, Min Gu, Yang Lü
Inhibition of endocytosis in an Alzheimer's disease (AD) model has been shown to be able to prevent amyloid β (Aβ)-induced damage and to exert a beneficial effect in treating AD. Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis. However, how AAK1 expression varies over the course of AD is unknown. In this study, we investigated AAK1 levels in AD model mice over time. Aβ1-42 was used to establish a mouse AD model, and the Morris water maze test was used to characterize the time course of Aβ1-42 -induced cognition changes...
May 17, 2018: Journal of Molecular Neuroscience: MN
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
#2
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/29768434/plasma-membrane-insertion-of-kca2-3-sk3-is-dependent-upon-the-snare-proteins-syntaxin-4-and-snap23
#3
Claudia A Bertuccio, Tony T Wang, Kirk L Hamilton, Diego J Rodriguez-Gil, Steven B Condliffe, Daniel C Devor
We previously demonstrated endocytosis of KCa2.3 is caveolin-1-, dynamin II- and Rab5-dependent. KCa2.3 then enters Rab35/EPI64C- and RME-1-containing recycling endosomes and is returned to the plasma membrane (PM). Herein, we report on the mechanism by which KCa2.3 is inserted into the PM during recycling and following exit from the Golgi. We demonstrate KCa2.3 colocalizes with SNAP-23 and Syntaxin-4 in the PM of HEK and endothelial cells by confocal immunofluorescence microscopy. We further show KCa2.3 can be co-immunoprecipitated with SNAP-23 and Syntaxin-4...
2018: PloS One
https://www.readbyqxmd.com/read/29760437/cd82-hypomethylation-is-essential-for-tuberculosis-pathogenesis-via-regulation-of-runx1-rab5-22
#4
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang
The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29749929/integration-of-two-rab5-groups-during-endosomal-transport-in-plants
#5
Emi Ito, Kazuo Ebine, Seung-Won Choi, Sakura Ichinose, Tomohiro Uemura, Akihiko Nakano, Takashi Ueda
RAB5 is a key regulator of endosomal functions in eukaryotic cells. Plants possess two different RAB5 groups, canonical and plant-unique types, which act via unknown counteracting mechanisms. Here, we identified an effector molecule of the plant-unique RAB5 in Arabidopsis thaliana , ARA6, which we designated PLANT-UNIQUE RAB5 EFFECTOR 2 (PUF2). Preferential colocalization with canonical RAB5 on endosomes and genetic interaction analysis indicated that PUF2 coordinates vacuolar transport with canonical RAB5, although PUF2 was identified as an effector of ARA6...
May 11, 2018: ELife
https://www.readbyqxmd.com/read/29746582/assembly-hub-function-of-er-localized-snare-proteins-in-biogenesis-of-tombusvirus-replication-compartment
#6
Zsuzsanna Sasvari, Nikolay Kovalev, Paulina Alatriste Gonzalez, Kai Xu, Peter D Nagy
Positive-strand RNA viruses assemble numerous membrane-bound viral replicase complexes within large replication compartments to support their replication in infected cells. Yet the detailed mechanism of how given subcellular compartments are subverted by viruses is incompletely understood. Although, Tomato bushy stunt virus (TBSV) uses peroxisomal membranes for replication, in this paper, we show evidence that the ER-resident SNARE (soluble NSF attachment protein receptor) proteins play critical roles in the formation of active replicase complexes in yeast model host and in plants...
May 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29740032/patient-derived-mutations-within-the-n-terminal-domains-of-p85%C3%AE-impact-pten-or-rab5-binding-and-regulation
#7
Paul Mellor, Jeremy D S Marshall, Xuan Ruan, Dielle E Whitecross, Rebecca L Ross, Margaret A Knowles, Stanley A Moore, Deborah H Anderson
The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29608571/endocytic-recycling-via-the-tgn-underlies-the-polarized-hyphal-mode-of-life
#8
Miguel Hernández-González, Ignacio Bravo-Plaza, Mario Pinar, Vivian de Los Ríos, Herbert N Arst, Miguel A Peñalva
Intracellular traffic in Aspergillus nidulans hyphae must cope with the challenges that the high rates of apical extension (1μm/min) and the long intracellular distances (>100 μm) impose. Understanding the ways in which the hyphal tip cell coordinates traffic to meet these challenges is of basic importance, but is also of considerable applied interest, as fungal invasiveness of animals and plants depends critically upon maintaining these high rates of growth. Rapid apical extension requires localization of cell-wall-modifying enzymes to hyphal tips...
April 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29603841/regulation-of-early-endosomes-across-eukaryotes-evolution-and-functional-homology-of-vps9-proteins
#9
Emily K Herman, Moazzam Ali, Mark C Field, Joel B Dacks
Endocytosis is a crucial process in eukaryotic cells. The GTPases Rab 5, 21 and 22 that mediate endocytosis are ancient eukaryotic features and all available evidence suggests conserved function. In animals and fungi, these GTPases are regulated in part by proteins possessing Vps9 domains. However, the diversity, evolution and functions of Vps9 proteins beyond animals or fungi are poorly explored. Here we report a comprehensive analysis of the Vps9 family of GTPase regulators, combining molecular evolutionary data with functional characterization in the non-opisthokont model organism Trypanosoma brucei...
March 30, 2018: Traffic
https://www.readbyqxmd.com/read/29573133/lipid-packing-defects-and-membrane-charge-control-rab-gtpase-recruitment
#10
Guillaume Kulakowski, Hugo Bousquet, Jean-Baptiste Manneville, Patricia Bassereau, Bruno Goud, Lena K Oesterlin
Specific intracellular localization of RAB GTPases has been reported to be dependent on protein factors but the contribution of the membrane physicochemical properties to this process has been poorly described. Here, we show that three RAB proteins (RAB1/RAB5/RAB6) preferentially bind in vitro to disordered and curved membranes, and that this feature is uniquely dependent on their prenyl group. Our results imply that the addition of a prenyl group confers to RAB proteins, and most probably also to other prenylated proteins, the ability to sense lipid packing defects induced by unsaturated conical-shaped lipids and curvature...
March 23, 2018: Traffic
https://www.readbyqxmd.com/read/29535423/jnk-and-yorkie-drive-tumor-progression-by-generating-polyploid-giant-cells-in-drosophila
#11
Bojie Cong, Shizue Ohsawa, Tatsushi Igaki
Epithelial cancer tissues often possess polyploid giant cells, which are thought to be highly oncogenic. However, the mechanisms by which polyploid giant cells are generated in tumor tissues and how such cells contribute to tumor progression remain elusive. We previously noticed in Drosophila imaginal epithelium that cells mutant for the endocytic gene rab5 exhibit enlarged nuclei. Here we find that mutations in endocytic 'neoplastic tumor-suppressor' genes, such as rab5, vps25, erupted, or avalanche result in generation of polyploid giant cells...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29514909/hiv-1-nef-antagonizes-serinc5-restriction-by-downregulation-of-serinc5-via-the-endosome-lysosome-system
#12
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/29507050/proteomics-of-aspergillus-fumigatus-conidia-containing-phagolysosomes-identifies-processes-governing-immune-evasion
#13
Hella Schmidt, Sebastian Vlaic, Thomas Krüger, Franziska Schmidt, Johannes Balkenhohl, Thomas Dandekar, Reinhard Guthke, Olaf Kniemeyer, Thorsten Heinekamp, Axel A Brakhage
Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing...
March 5, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29497081/hypoxia-induced-exosome-secretion-promotes-survival-of-african-american-and-caucasian-prostate-cancer-cells
#14
Gati K Panigrahi, Prakash P Praharaj, Taylor C Peak, Jessica Long, Ravi Singh, Johng S Rhim, Zakaria Y Abd Elmageed, Gagan Deep
African American men in the United States have higher mortality due to prostate cancer (PCa) compared to other races. One reason for this disparity is the lack of in-depth understanding of the PCa biology in African Americans. For example, hypoxia in prostate tumor microenvironment is associated with adverse prognosis; still, no hypoxia-related studies have been reported in African Americans. Here, we compared African-American and Caucasian PCa cells for exosome secretion under normoxic (21% O2 ) and hypoxic (1% O2 ) conditions...
March 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29486010/the-cellular-uptake-of-angiogenin-an-angiogenic-and-neurotrophic-factor-is-through-multiple-pathways-and-largely-dynamin-independent
#15
Ross Ferguson, Vasanta Subramanian
Angiogenin (ANG), a member of the RNase superfamily (also known as RNase 5) has neurotrophic, neuroprotective and angiogenic activities. Recently it has also been shown to be important in stem cell homeostasis. Mutations in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD). ANG is a secreted protein which is taken up by cells and translocated to the nucleus. However, the import pathway/s through which ANG is taken up is/are still largely unclear...
2018: PloS One
https://www.readbyqxmd.com/read/29485922/loss-of-vps9b-enhances-vps9a-2-phenotypes
#16
Mads Eggert Nielsen, Hans Thordal-Christensen
Plant innate immunity enables plants to defend themselves against infectious pathogens. While membrane trafficking and release of exosomes are considered vital for correct execution of innate immunity, the mechanisms behind remain elusive. Recently, we have shown that VPS9a, the general guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against powdery mildew fungi in Arabidopsis thaliana. Yet, the Arabidopsis genome contains a close homologue of VPS9a, which potentially plays specific roles in innate immunity...
April 3, 2018: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29469808/rab5-and-alsin-regulate-stress-activated-cytoprotective-signaling-on-mitochondria
#17
FoSheng Hsu, Stephanie Spannl, Charles Ferguson, Anthony A Hyman, Robert G Parton, Marino Zerial
Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. Thus, it is fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosomal contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to mitochondria upon oxidative stress. This process is reversible and accompanied by an increase in Rab5-positive endosomes in contact with mitochondria...
February 22, 2018: ELife
https://www.readbyqxmd.com/read/29463724/distinct-sets-of-tethering-complexes-snare-complexes-and-rab-gtpases-mediate-membrane-fusion-at-the-vacuole-in-arabidopsis
#18
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/29444302/rab-gtpases-in-the-basal-land-plant-marchantia-polymorpha
#19
Naoki Minamino, Takehiko Kanazawa, Atsuko Era, Kazuo Ebine, Akihiko Nakano, Takashi Ueda
The RAB GTPase is an evolutionarily conserved machinery component of membrane trafficking, which is the fundamental system for cell viability and higher order biological functions. The composition of RAB GTPases in each organism is closely related to the complexity and organization of the membrane trafficking pathway, which has been developed uniquely to realize the organism-specific membrane trafficking system. Comparative genomics has suggested that terrestrialization and/or multicellularization were associated with the expansion of membrane trafficking pathways in green plants, which has yet to be validated in basal land plant lineages...
April 1, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29438268/endocytosis-of-red-blood-cell-microparticles-by-pulmonary-endothelial-cells-is-mediated-by-rab5
#20
Young Kim, William A Abplanalp, Andrew D Jung, Rebecca M Schuster, Alex B Lentsch, Erich Gulbins, Charles C Caldwell, Timothy A Pritts
Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6...
March 2018: Shock
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