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https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#1
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
#2
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/28623232/the-ring-finger-and-pdz-domain-containing-protein-pdzrn3-controls-localization-of-the-mg-2-regulator-claudin-16-in-renal-tube-epithelial-cells
#3
Kana Marunaka, Chisa Furukawa, Naoko Fujii, Toru Kimura, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Naohiko Anzai, Yasuhiro Yamazaki, Masahiko Yamaguchi, Akira Ikari
Ion exchange in the renal tubules is fundamental to the maintenance of physiological ion levels. Claudin-16 (CLDN16) regulates the paracellular reabsorption of Mg(2+) in the thick ascending limb of Henle's loop in the kidney, with dephosphorylation of CLDN16 increasing its intracellular distribution and decreasing paracellular Mg(2+) permeability. CLDN16 is located in the tight junctions, but the mechanism regulating its localization is unclear. Using yeast two-hybrid systems, we found that CLDN16 binds to PDZRN3, a protein containing both RING-finger and PDZ-domains...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28600323/rab7-palmitoylation-is-required-for-efficient-endosome-to-tgn-trafficking
#4
Graziana Modica, Olga Skorobogata, Etienne Sauvageau, Adriano Vissa, Christopher M Yip, Peter K Kim, Hugo Wurtele, Stephane Lefrancois
Retromer is a multimeric protein complex that mediates endosome-to-TGN and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 to coordinate endosome-to- TGN trafficking of cargo-receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins such as the epidermal growth factor receptor. We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28589907/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#5
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588238/disruption-of-small-gtpase-rab7-exacerbates-the-severity-of-acute-pancreatitis-in-experimental-mouse-models
#6
Kenichi Takahashi, Hirosato Mashima, Kouichi Miura, Daichi Maeda, Akiteru Goto, Takashi Goto, Ge-Hong Sun-Wada, Yoh Wada, Hirohide Ohnishi
Although aberrations of intracellular vesicle transport systems towards lysosomes including autophagy and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7(Δpan)) mice. In Rab7(Δpan) pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28570716/host-lipid-droplets-an-important-source-of-lipids-salvaged-by-the-intracellular-parasite-toxoplasma-gondii
#7
Sabrina J Nolan, Julia D Romano, Isabelle Coppens
Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28554874/free-cholesterol-accumulation-in-liver-sinusoidal-endothelial-cells-exacerbates-acetaminophen-hepatotoxicity-via-tlr9-signaling
#8
Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Shigeaki Hida, Yoshikiyo Okada, Chie Kurihara, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Hidetsugu Saito, Toshifumi Hibi, Soichiro Miura, Ryota Hokari, Takanori Kanai
BACKGROUND & AIMS: Although obesity is a risk factor for acute liver failure, the pathogenic mechanisms are not yet fully understood. High cholesterol (HC) intake, which often underlies obesity, is suggested to play a role in the mechanism. We aimed to elucidate the effect of HC diet on acetaminophen-induced acute liver injury, the most frequent cause of acute liver failure in the USA. METHODS: C57BL/6 Toll-like receptor 9 (TLR9) knockout (Tlr9(-/-)) mice and their Tlr9(+/+) littermates were fed an HC diet for 4 weeks and then treated with acetaminophen...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28546026/the-crustin-like-peptide-plays-opposite-role-in-shrimp-immune-response-to-vibrio-alginolyticus-and-white-spot-syndrome-virus-wssv-infection
#9
Baozhen Sun, Zhi Wang, Fei Zhu
Crustin is an antimicrobial peptide (AMP) that plays a key role in innate immunity of crustaceans. In this study, we cloned the entire 660 bp crustin-like sequence with a 507 bp open reading frame encoding a 168 amino acid from Marsupenaeus japonicus. The crustin-like gene was primarily expressed in gills and over-expressed in shrimp hemocytes after challenge with WSSV or Vibrio alginolyticus. After knockdown crustin-like gene using specific double-stranded RNA (CRU-dsRNA), IMD, Rab7, L-lectin, mitogen-activated protein kinase, p53, prophenoloxidase and Rho were down-regulated and nitric oxide synthase, myosin and tumor necrosis factor-α were up-regulated in hemocytes at 24 h post dsRNA treatment...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28539733/molecular-docking-of-phytoligands-to-the-viral-protein-receptor-p-monodon-rab7
#10
Jerrine Joseph, Raj Bhaskaran, Muthusamy Kaliraj, Muthiyah Muthuswamy, Arumugam Suresh
The development of shrimp aquaculture has been severely affected by viral diseases resulting in a huge economic burden to the industry. White spot disease (WSD) has caused severe mortality in farmed shrimp in many countries. Globally aquaculture industries face huge economic losses due to rapid spread of White Spot Syndrome Virus (WSSV) disease that can cause 100% mortality in a short period of 3-10 days. In the present study in order to prevent the spread of WSSV disease in shrimps, the receptor, PmRab7 has been chosen as the drug target...
2017: Bioinformation
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#11
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483915/rab2-promotes-autophagic-and-endocytic-lysosomal-degradation
#12
Péter Lőrincz, Sarolta Tóth, Péter Benkő, Zsolt Lakatos, Attila Boda, Gábor Glatz, Martina Zobel, Sara Bisi, Krisztina Hegedűs, Szabolcs Takáts, Giorgio Scita, Gábor Juhász
Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting...
May 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28465352/cystinosin-the-small-gtpase-rab11-and-the-rab7-effector-rilp-regulate-intracellular-trafficking-of-the-chaperone-mediated-autophagy-receptor-lamp2a
#13
Jinzhong Zhang, Jennifer L Johnson, Jing He, Gennaro Napolitano, Mahalakshmi Ramadass, Celine Rocca, William B Kiosses, Cecilia Bucci, Qisheng Xin, Evripidis Gavathiotis, Ana María Cuervo, Stephanie Cherqui, Sergio D Catz
The lysosomal storage disease cystinosis, caused by cystinosin-deficiency, is characterized by cell malfunction, tissue failure and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A, and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28428220/cmtm3-cklf-like-marvel-transmembrane-domain-3-mediates-angiogenesis-by-regulating-cell-surface-availability-of-ve-cadherin-in-endothelial-adherens-junctions
#14
Ihsan Chrifi, Laura Louzao-Martinez, Maarten Brandt, Christian G M van Dijk, Petra Burgisser, Changbin Zhu, Johan M Kros, Dirk J Duncker, Caroline Cheng
OBJECTIVE: Decrease in VE-cadherin adherens junctions reduces vascular stability, whereas disruption of adherens junctions is a requirement for neovessel sprouting during angiogenesis. Endocytosis plays a key role in regulating junctional strength by altering bioavailability of cell surface proteins, including VE-cadherin. Identification of new mediators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we assessed the function of CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously identified as highly expressed in Flk1(+) endothelial progenitor cells during embryonic development...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28422978/the-escrt-regulator-did2-maintains-the-balance-between-long-distance-endosomal-transport-and-endocytic-trafficking
#15
Carl Haag, Thomas Pohlmann, Michael Feldbrügge
In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#16
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415719/endosomal-sorting-and-c-cbl-targeting-of-paxillin-to-autophagosomes-regulate-cell-matrix-adhesion-turnover-in-human-breast-cancer-cells
#17
Chia-Hao Chang, Krikor Bijian, Dinghong Qiu, Jie Su, Amine Saad, Michael S Dahabieh, Wilson H Miller, Moulay A Alaoui-Jamali
Post-translational mechanisms regulating cell-matrix adhesion turnover during cell locomotion are not fully elucidated. In this study, we uncovered an essential role of Y118 site-specific tyrosine phosphorylation of paxillin, an adapter protein of focal adhesion complexes, in paxillin recruitment to autophagosomes to trigger turnover of peripheral focal adhesions in human breast cancer cells. We demonstrate that the Rab-7 GTPase is a key upstream regulator of late endosomal sorting of tyrosine118-phosphorylated paxillin, which is subsequently recruited to autophagosomes via the cargo receptor c-Cbl...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396666/dynamic-changes-in-the-intracellular-association-of-selected-rab-small-gtpases-with-mhc-class-ii-and-dm-during-dendritic-cell-maturation
#18
Gibrán Pérez-Montesinos, Orestes López-Ortega, Jessica Piedra-Reyes, Laura C Bonifaz, José Moreno
Antigen processing for presentation by major histocompatibility complex class II (MHCII) molecules requires the latter to travel through the endocytic pathway together with its chaperons: the invariant chain (Ii) and DM. Nevertheless, the nature of the compartments where MHCII molecules travel to acquire peptides lacks definition regarding molecules involved in intracellular vesicular trafficking, such as Rab small GTPases. We aimed to define which Rab proteins are present during the intracellular transport of MHCII, DM, and Ii through the endocytic pathway on their route to the cell surface during dendritic cell (DC) maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28394828/rab7-a-novel-redox-target-that-modulates-inflammatory-pain-processing
#19
Wiebke Kallenborn-Gerhardt, Christine V Möser, Jana E Lorenz, Mirco Steger, Juliana Heidler, Reynir Scheving, Jonas Petersen, Lea Kennel, Cathrin Flauaus, Ruirui Lu, Aimee L Edinger, Irmgard Tegeder, Gerd Geisslinger, Heinrich Heide, Ilka Wittig, Achim Schmidtko
Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice...
July 2017: Pain
https://www.readbyqxmd.com/read/28348980/overexpression-of-the-endosomal-anion-proton-exchanger-clc-5-increases-cell-susceptibility-toward-clostridium-difficile-toxins-tcda-and-tcdb
#20
Frederike Ruhe, Alexandra Olling, Rasmus Abromeit, Dennis Rataj, Matthias Grieschat, Andre Zeug, Ralf Gerhard, Alexi Alekov
Virulent C. difficile toxins TcdA and TcdB invade host intestinal epithelia by endocytosis and use the acidic environment of intracellular vesicles for further processing and activation. We investigated the role of ClC-5, a chloride/proton exchanger expressed in the endosomes of gastrointestinal epithelial cells, in the activation and processing of C. difficile toxins. Enhanced intoxication by TcdA and TcdB was observed in cells expressing ClC-5 but not ClC-4, another chloride/proton exchanger with similar function but different localization...
2017: Frontiers in Cellular and Infection Microbiology
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