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https://www.readbyqxmd.com/read/29343549/intracellular-vesicle-trafficking-plays-an-essential-role-in-mitochondrial-quality-control
#1
Mike Gerards, Giuseppe Cannino, Jose M González de Cózar, Howard T Jacobs
The Drosophila gene products Bet1, Slh and CG10144, predicted to function in intracellular vesicle trafficking, were previously found to be essential for mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to maintain mitochondrial functions. In their absence, mitochondrial content, membrane potential and respiration became abnormal, accompanied by mitochondrial proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry showed that both Slh and Bet1 are localized at the Golgi, together with a proportion of Rab5-positive vesicles...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29331581/identification-and-characterization-of-arginine-finger-like-motifs-and-endosome-lysosome-basolateral-sorting-signals-within-ectopically-expressed-cira-a-coxiella-burnetii-type-iv-secreted-effector-protein
#2
Mary M Weber, Robert Faris, Erin J van Schaik, James E Samuel
Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro...
January 10, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#3
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29314494/dysregulation-of-rab5-mediated-endocytic-pathways-in-alzheimer-s-disease
#4
REVIEW
Wei Xu, Fang Fang, Jianqing Ding, Chengbiao Wu
Increasing evidence has pointed to that dysregulation of the endo-lysosomal system is an early cellular phenotype of pathogenesis for Alzheimer's disease (AD). Rab5, a small GTPase, plays a critical role in mediating these processes. Abnormal overactivation of Rab5 has been observed in post-mortem brain samples of Alzheimer's patients as well as brain samples of mouse models of AD. Recent genome-wide association studies of Alzheimer's disease have identified RIN3 (Ras and Rab Interactor 3) as a novel risk factor for the disease...
January 3, 2018: Traffic
https://www.readbyqxmd.com/read/29277005/landmarks-of-endosomal-remodeling-in-the-early-phase-of-cytomegalovirus-infection
#5
Ljerka Karleuša, Hana Mahmutefendić, Maja Ilić Tomaš, Gordana Blagojević Zagorac, Pero Lučin
Cytomegaloviruses (CMVs) extensively rearrange the cellular membrane system to develop assembly compartment (AC), but the earliest events in this process are poorly characterized. Here, we demonstrate that murine CMV (MCMV) infection restrains endosomal trafficking of cargo molecules that travel along the recycling (TfR and MHC-I) and the late endosomal (EGFR, M6PR, Lamp1) circuit. Internalized cargo accumulates in Arf6-, Rab5-, Rab22A-, and Rab11-positive and Rab35-, Rab8-, and Rab10-negative juxtanuclear endosomes, suggesting the disruption of Arf/Rab regulatory cascade at the stage of sorting endosomes and the endosomal recycling compartment...
December 22, 2017: Virology
https://www.readbyqxmd.com/read/29247183/rab-gtpase-binding-effector-protein-2-rabep2-is-a-primed-substrate-for-glycogen-synthase-kinase-3-gsk3
#6
Lisa Logie, Lidy Van Aalten, Axel Knebel, Thomas Force, C James Hastie, Hilary MacLauchlan, David G Campbell, Robert Gourlay, Alan Prescott, Jane Davidson, Will Fuller, Calum Sutherland
Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29237927/distinct-rab7-related-endosomal-autophagic-lysosomal-dysregulation-observed-in-cortex-and-hippocampus-in-appswe-psen1de9-mouse-model-of-alzheimer-s-disease
#7
Li Ba, Xiao-Hua Chen, Yan-Lin Chen, Qing Nie, Zhi-Jun Li, Feng-Fei Ding, Min Zhang
BACKGROUND: Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction. METHODS: We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29236694/dynamics-of-phosphoinositide-conversion-in-clathrin-mediated-endocytic-traffic
#8
Kangmin He, Robert Marsland Iii, Srigokul Upadhyayula, Eli Song, Song Dang, Benjamin R Capraro, Weiming Wang, Wesley Skillern, Raphael Gaudin, Minghe Ma, Tom Kirchhausen
Vesicular carriers transport proteins and lipids from one organelle to another, recognizing specific identifiers for the donor and acceptor membranes. Two important identifiers are phosphoinositides and GTP-bound GTPases, which provide well-defined but mutable labels. Phosphatidylinositol and its phosphorylated derivatives are present on the cytosolic faces of most cellular membranes. Reversible phosphorylation of its headgroup produces seven distinct phosphoinositides. In endocytic traffic, phosphatidylinositol-4,5-biphosphate marks the plasma membrane, and phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate mark distinct endosomal compartments...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29210146/central-administration-of-galanin-n-terminal-fragment-1-15-decreases-the-voluntary-alcohol-intake-in-rats
#9
Carmelo Millón, Antonio Flores-Burgess, Estela Castilla-Ortega, Belén Gago, María García-Fernandez, Antonia Serrano, Fernando Rodriguez de Fonseca, José Angel Narváez, Kjell Fuxe, Luis Santín, Zaida Díaz-Cabiale
Alcohol consumption is considered a major risk factor for disease and mortality worldwide. In the absence of effective treatments in alcohol use disorders, it is important to find new biological targets that could modulate alcohol consumption. We tested the role of the N-terminal galanin fragment (1-15) [GAL(1-15)] in voluntary ethanol consumption in rats using the two-bottle choice paradigm as well as compare the effects of GAL(1-15) with the whole molecule of GAL. We describe for the first time that GAL(1-15), via central mechanisms, induces a strong reduction in preference and ethanol consumption in rats...
December 6, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29174139/altered-tgf-%C3%AE-endocytic-trafficking-contributes-to-the-increased-signaling-in-marfan-syndrome
#10
Anna-Maria Siegert, Carla Serra-Peinado, Enric Gutiérrez-Martínez, Fernando Rodríguez-Pascual, Isabel Fabregat, Gustavo Egea
The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation...
November 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29170408/identification-of-the-binding-sites-on-rab5-and-p110beta-phosphatidylinositol-3-kinase
#11
Dielle E Whitecross, Deborah H Anderson
Rab5 is a small monomeric GTPase that mediates protein trafficking during endocytosis. Inactivation of Rab5 by GTP hydrolysis causes a conformational change that masks binding sites on its "switch regions" from downstream effectors. The p85 subunit of phosphatidylinositol 3-kinase (PI3K) is a GTPase activating protein (GAP) towards Rab5. Whereas p85 can bind with both Rab5-GTP and Rab5-GDP, the PI3K catalytic subunit p110β binds only Rab5-GTP, suggesting it interacts with the switch regions. Thus, the GAP functions of the catalytic arginine finger (from p85) and switch region stabilization (from p110β) may be provided by both proteins, acting together...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150640/early-endosome-motility-mediates-%C3%AE-amylase-production-and-cell-differentiation-in-aspergillus-oryzae
#12
Yusuke Togo, Yujiro Higuchi, Yoshinori Katakura, Kaoru Takegawa
Recent research in filamentous fungi has revealed that the motility of an endocytic organelle early endosome (EE) has a versatile role in many physiological functions. Here, to further examine the motility of EEs in the industrially important fungus Aspergillus oryzae, we visualized these organelles via the Rab5 homolog AoRab5 and identified AoHok1, a putative linker protein between an EE and a motor protein. The Aohok1 disruptant showed retarded mycelial growth and no EE motility, in addition to an apical accumulation of EEs and peroxisomes...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127297/rab5-is-critical-for-snap23-regulated-granule-granule-fusion-during-compound-exocytosis
#13
Ofir Klein, Amit Roded, Neta Zur, Nurit P Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J Galli, Ronit Sagi-Eisenberg
Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117102/mechanisms-of-entry-and-endosomal-pathway-of-african-swine-fever-virus
#14
REVIEW
Elena G. Sánchez, Daniel Pérez-Núñez, Yolanda Revilla
African Swine Fever Virus (ASFV) causes a serious swine disease that is endemic in Africa and Sardinia and presently spreading in Russia and neighboring countries, including Poland and recently, the Czech Republic. This uncontrolled dissemination is a world-wide threat, as no specific protection or vaccine is available. ASFV is a very complex icosahedral, enveloped virus about 200 nm in diameter, which infects several members of pigs. The virus enters host cells by receptor-mediated endocytosis that depends on energy, vacuolar pH and temperature...
November 8, 2017: Vaccines
https://www.readbyqxmd.com/read/29099266/calpain2-mediates-rab5-driven-focal-adhesion-disassembly-and-cell-migration
#15
Pablo A Mendoza, Patricio Silva, Jorge Díaz, Cecilia Arriagada, Jimena Canales, Oscar Cerda, Vicente A Torres
The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitate with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions...
November 3, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29095572/structural-plasticity-mediates-distinct-gap-dependent-gtp-hydrolysis-mechanisms-in-rab33-and-rab5
#16
Soneya Majumdar, Abhishek Acharya, Balaji Prakash
The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic Gln, provided in-cis by the GTPase, and an Arginine supplied in-trans by a GTPase Activating Protein (GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis...
November 2, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29065764/recognition-and-stabilization-of-geranylgeranylated-human-rab5-by-the-gdp-dissociation-inhibitor-gdi
#17
Eileen Edler, Matthias Stein
The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post-translationally modified by covalent attachment of two geranylgeranyl (GG) chains to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and serves to release it into the cytoplasm where it is kept in a soluble state. A detailed new structural and dynamic model for human Rab5(GDP) recognition and binding with human GDI at the early endosome membrane and in its dissociated state is presented...
October 25, 2017: Small GTPases
https://www.readbyqxmd.com/read/29058791/in-vitro-and-in-vivo-effect-of-pd-1-pd-l1-blockade-on-microglia-macrophage-activation-and-t-cell-subset-balance-in-cryptococcal-meningitis
#18
Yuan-Mei Che, Yi Zhang, Ming Li, Xiao-Peng Li, Lun-Li Zhang
This study aimed to investigate the PD-1/ PD-L1 signaling pathway and its effects the activation of microglia/macrophage and balancing T cell subsets in cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy individuals were recruited for the study. The CM patients were treated with amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal control, CM model, CM + AmB, sham, and CM + PD-1 antibodies (Ab) groups. CD4+ and CD8+ T cells as well as microglia/macrophages were analyzed by means of flow cytometry...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29056935/the-atypical-receptor-ccrl2-c-c-chemokine-receptor-like-2-does-not-act-as-a-decoy-receptor-in-endothelial-cells
#19
Chiara Mazzotti, Vincenzo Gagliostro, Daniela Bosisio, Annalisa Del Prete, Laura Tiberio, Marcus Thelen, Silvano Sozzani
C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family. ACKRs bind chemokines but do not activate G protein-dependent signaling or cell functions. ACKRs were shown to regulate immune functions in vivo by their ability to scavenge chemokines from the local environment. This study was performed to investigate whether CCRL2 shares two of the main characteristics of ACKRs, namely the ability to internalize and scavenge the ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29031718/g%C3%AE-s-regulates-glucagon-like-peptide-1-receptor-mediated-cyclic-amp-generation-at%C3%A2-rab5-endosomal-compartment
#20
Shravan Babu Girada, Ramya S Kuna, Shilpak Bele, Zhimeng Zhu, N R Chakravarthi, Richard D DiMarchi, Prasenjit Mitra
OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined...
October 2017: Molecular Metabolism
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