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https://www.readbyqxmd.com/read/28317806/mycobacterium-lepraemurium-uses-tlr-6-and-mr-but-not-lipid-rafts-or-dc-sign-to-gain-access-into-mouse-macrophages
#1
Mayra Silva-Miranda, Patricia Arce-Paredes, Oscar Rojas-Espinosa
OBJECTIVE/BACKGROUND: Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. MATERIALS AND METHODS: Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28315838/germline-proliferation-is-regulated-by-somatic-endocytic-genes-via-jnk-and-bmp-signaling-in-drosophila
#2
Yaning Tang, Qing Geng, Di Chen, Shaowei Zhao, Xian Liu, Zhaohui Wang
Signals derived from the microenvironment contribute greatly to tumorigenesis. The underlying mechanism requires thorough investigation. Here, we use Drosophila testis as a model system to address this question, taking the advantage of the ease to distinguish germline and somatic cells and to track the cell numbers. In an EMS mutagenesis screen, we identified Rab5, a key factor in endocytosis, for its non-autonomous role in germline proliferation. The disruption of Rab5 in somatic cyst cells, which escort the development of germline lineage, induced the over-proliferation of under-differentiated but genetically wild-type germ cells...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#3
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- and milli-calpain. Upon the inhibition of the endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1 dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1 containing vesicles with LC3 bodies in control cells. On the opposite, CAPNS1 depletion is coupled to an accumulation of LC3 bodies and Rab5 early endosomes...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28270608/rab5-regulated-endocytosis-plays-a-crucial-role-in-apical-extrusion-of-transformed-cells
#4
Sayaka Saitoh, Takeshi Maruyama, Yuta Yako, Mihoko Kajita, Yoichiro Fujioka, Yusuke Ohba, Nobuhiro Kasai, Natsu Sugama, Shunsuke Kon, Susumu Ishikawa, Takashi Hayashi, Tomohiro Yamazaki, Masazumi Tada, Yasuyuki Fujita
Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28264927/missing-in-metastasis-protein-downregulates-cxcr4-by-promoting-ubiquitination-and-interaction-with-small-rab-gtpases
#5
Lushen Li, Shaneen S Baxter, Ning Gu, Min Ji, Xi Zhan
Surface expression of chemokine receptor CXCR4 is downregulated by MIM, a member of the inverse BAR (I-BAR) domain protein family that recognizes and generates membranes with negative curvatures. Yet, the mechanism for the regulation is unknown. Here, we showed that MIM formed a complex with CXCR4 via binding to E3 ubiquitin ligase AIP4 in response to SDF-1. Overexpression of MIM promoted CXCR4 ubiquitination, inhibited cellular response to SDF-1, caused accumulation and aggregation of MVBs in the cytoplasm, and promoted CXCR4 sorting into MVBs in a manner depending on binding to AIP4...
March 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28242757/acute-acinar-pancreatitis-blocks-vesicle-associated-membrane-protein-8-vamp8-dependent-secretion-resulting-in-intracellular-trypsin-accumulation
#6
Scott W Messenger, Elaina K Jones, Conner L Holthaus, Diana D H Thomas, Michelle M Cooley, Jennifer A Byrne, Olga A Mareninova, Anna S Gukovskaya, Guy E Groblewski
Zymogen secretory granules in pancreatic acinar cells express two vesicle associated membrane proteins (VAMP), VAMP2 and 8, each controlling 50% of stimulated secretion. Analysis of secretion kinetics identified a first-phase (0 - 2 min) mediated by VAMP2, and second- (2 - 10 min) and third-phases (10- 30 min) mediated by VAMP8. Induction of acinar pancreatitis by supramaximal cholecystokinin (CCK-8) stimulation inhibits VAMP8-mediated second- and third-phase, but not VAMP2-mediated first-phase secretion. Elevation of cAMP during supramaximal CCK-8 mitigates third-phase secretory inhibition and acinar damage caused by the accumulation of prematurely activated trypsin...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28197146/the-c-terminus-of-epstein-barr-virus-brrf2-is-required-for-its-proper-localization-and-efficient-virus-production
#7
Takahiro Watanabe, Keiya Sakaida, Masahiro Yoshida, H M Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura, Takayuki Murata
Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with several malignancies. We reported previously that an EBV lytic gene product BRRF2 is involved in the maturation of progeny virus. To analyze the domain(s) needed for efficient production of progeny, we prepared a series of deletion mutants and found two functional domains in the N- and C-terminal regions by complementation assays. Immunofluorescence analyses revealed that BRRF2 lacking the C-terminal region demonstrated aberrant localization in both the nucleus and cytoplasm, whereas wild-type BRRF2 was localized predominantly in the cytoplasm...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28180992/comprehensive-functional-analysis-of-rab-gtpases-in-drosophila-nephrocytes
#8
Yulong Fu, Jun-Yi Zhu, Fujian Zhang, Adam Richman, Zhanzheng Zhao, Zhe Han
The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity...
February 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28176461/high-resolution-localization-of-rab5-eea1-and-nectin-3-to-tubulobulbar-complexes-in-the-rat-testis
#9
Arlo Adams, A Wayne Vogl
Tubulobulbar complexes are clathrin/actin-based structures that internalize intercellular junctions in the testis. They resemble coated pits with extremely long necks that are cuffed by dendritic actin networks. As the structures mature, a swollen region or bulb develops near the end of each complex. The bulbs lack actin cuffs and are closely associated with cisternae of endoplasmic reticulum. The bulbs expand and are internalized and enter endocytic compartments of the Sertoli cell. Previous immunofluorescence studies have demonstrated that markers for early endosomes (Rab5 and EEA1) are associated with tubulobulbar complexes and are localized at or near the ends of the structures...
February 8, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28134239/a-rab5-endosomal-pathway-mediates-parkin-dependent-mitochondrial-clearance
#10
Babette C Hammerling, Rita H Najor, Melissa Q Cortez, Sarah E Shires, Leonardo J Leon, Eileen R Gonzalez, Daniela Boassa, Sébastien Phan, Andrea Thor, Rebecca E Jimenez, Hong Li, Richard N Kitsis, Gerald W Dorn Ii, Junichi Sadoshima, Mark H Ellisman, Åsa B Gustafsson
Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28131869/quantifying-receptor-trafficking-and-colocalization-with-confocal-microscopy
#11
Jeremy A Pike, Iain B Styles, Joshua Z Rappoport, John K Heath
Confocal microscopy is a powerful tool for the study of cellular receptor trafficking and endocytosis. Unbiased and robust image analysis workflows are required for the identification, and study, of aberrant trafficking. After a brief review of related strategies, identifying both good and bad practice, custom workflows for the analysis of live cell 3D time-lapse data are presented. Strategies for data pre-processing, including denoising and background subtraction are considered. We use a 3D level set protocol to accurately segment cells using only the signal from fluorescently labelled receptor...
January 26, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28119397/misdirection-of-endosomal-trafficking-mediated-by-herpes-simplex-virus-encoded-glycoprotein-b
#12
Naima Niazy, Sebastian Temme, Derya Bocuk, Carmen Giesen, Angelika König, Nadine Temme, Angelique Ziegfeld, Tone F Gregers, Oddmund Bakke, Thorsten Lang, Anna M Eis-Hübinger, Norbert Koch
Herpes simplex virus (HSV)-encoded glycoprotein B (gB) is the most abundant protein in the viral envelope and promotes fusion of the virus with the cellular membrane. In the present study, we found that gB impacts on the major histocompatibility complex (MHC)-II pathway of antigen presentation by fostering homotypic fusion of early endosomes and trapping MHC-II molecules in these altered endosomes. By using an overexpression approach, we demonstrated that transient expression of gB induces giant vesicles of early endosomal origin, which contained Rab5, early endosomal antigen 1 (EEA1), large amounts of MHC-II molecules [human leukocyte antigen (HLA)-DR, and HLA-DM] but no CD63...
January 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28103577/association-of-rab5-overexpression-in-pancreatic-cancer-with-cancer-progression-and-poor-prognosis-via-e-cadherin-suppression
#13
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/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#14
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28076778/axl-mediates-zika-virus-entry-in-human-glial-cells-and-modulates-innate-immune-responses
#15
Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, Ali Amara
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28056926/edible-bird-s-nest-modulate-intracellular-molecular-pathways-of-influenza-a-virus-infected-cells
#16
Amin Haghani, Parvaneh Mehrbod, Nikoo Safi, Fadzilah A'ini Abd Kadir, Abdul Rahman Omar, Aini Ideris
BACKGROUND: Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized. METHODS: In this study, EBNs that underwent different enzymatic preparation were tested against IAV infected cells. 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50) of the EBNs against IAV strain A/Puerto Rico/8/1934(H1N1) were determined by HA and MTT assays...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28051187/architecture-and-mechanism-of-the-late-endosomal-rab7-like-ypt7-guanine-nucleotide-exchange-factor-complex-mon1-ccz1
#17
Stephan Kiontke, Lars Langemeyer, Anne Kuhlee, Saskia Schuback, Stefan Raunser, Christian Ungermann, Daniel Kümmel
The Mon1-Ccz1 complex (MC1) is the guanine nucleotide exchange factor (GEF) for the Rab GTPase Ypt7/Rab7 and is required for endosomal maturation and fusion at the vacuole/lysosome. Here we present the overall architecture of MC1 from Chaetomium thermophilum, and in combining biochemical studies and mutational analysis in yeast, we identify the domains required for catalytic activity, complex assembly and localization of MC1. The crystal structure of a catalytic MC1 core complex bound to Ypt7 provides mechanistic insight into its function...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28003220/recycling-of-apolipoprotein-a-after-plgrkt-mediated-endocytosis-of-lipoprotein-a
#18
Monika Sharma, Gregory M Redpath, Michael J Williams, Sally P McCormick
RATIONALE: Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL)-like lipoprotein and important cardiovascular risk factor whose cognate receptor and intracellular fate remains unknown. OBJECTIVE: Our study aimed to determine the intracellular trafficking pathway for Lp(a) and the receptor responsible for its uptake in liver cells. METHODS AND RESULTS: Human hepatoma (HepG2) cells were treated with Lp(a) purified from human plasma and Lp(a) uptake studied using western blot analysis and intracellular localisation of Lp(a) by confocal microscopy...
December 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27903237/leucine-rich-repeat-kinase-2-lrrk2-regulates-%C3%AE-synuclein-clearance-in-microglia
#19
Tatsunori Maekawa, Toshikuni Sasaoka, Sadahiro Azuma, Takafumi Ichikawa, Heather L Melrose, Matthew J Farrer, Fumiya Obata
BACKGROUND: α-Synuclein (αSYN) has been genetically implicated in familial and sporadic Parkinson's disease (PD), and is associated with disease susceptibility, progression and pathology. Excess amounts of αSYN are toxic to neurons. In the brain, microglial αSYN clearance is closely related to neuronal survival. Leucine-rich repeat kinase 2 (LRRK2) is the one of the other genes implicated in familial and sporadic PD. While LRRK2 is known to be expressed in microglia, its true function remains to be elucidated...
November 30, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#20
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
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