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Endosomal trafficking

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https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#1
Mads Eggert Nielsen, Gerd Jürgens, Hans Thordal-Christensen
Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for pre-invasive immunity; in post-invasive immunity the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against a non-adapted powdery mildew fungus (Blumeria graminis f...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28806752/the-escrt-iii-pathway-facilitates-cardiomyocyte-release-of-cbin1-containing-microparticles
#2
Bing Xu, Ying Fu, Yan Liu, Sosse Agvanian, Robert C Wirka, Rachel Baum, Kang Zhou, Robin M Shaw, TingTing Hong
Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold- generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus...
August 14, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28802715/elucidating-virus-entry-using-a-tetracysteine-tagged-virus
#3
REVIEW
Bjorn-Patrick Mohl, Polly Roy
Fluorescent tags constitute an invaluable tool in facilitating a deeper understanding of the mechanistic processes governing virus-host interactions. However, when selecting a fluorescent tag for in vivo imaging of cells, a number of parameters and aspects must be considered. These include whether the tag may affect and interfere with protein conformation or localization, cell toxicity, spectral overlap, photo-stability and background. Cumulatively, these constitute challenges to be overcome. Bluetongue virus (BTV), a member of the Orbivirus genus in the Reoviridae family, is a non-enveloped virus that is comprised of two architecturally complex capsids...
August 9, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28800156/quantitative-dextran-trafficking-to-the-coxiella-burnetii-parasitophorous-vacuole
#4
Seth Winfree, Stacey D Gilk
The gram-negative bacterium Coxiella burnetii causes human Q fever, a disease characterized by a debilitating flu-like illness in acute cases and endocarditis in chronic patients. An obligate intracellular pathogen, Coxiella burnetii survives within a large, lysosome-like vacuole inside the host cell. A unique feature of the Coxiella parasitophorous vacuole (PV) is high levels of fusion with the host endocytic pathway, with PV-endosome fusion critical for Coxiella survival within the host cell. This unit describes quantitating PV-endosome fusion by measuring delivery of the fluid phase endosome marker dextran to the PV using live cell imaging...
August 11, 2017: Current Protocols in Microbiology
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#5
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28797971/modified-pamam-dendrimer-with-4-carbomethoxypyrrolidone-surface-groups-its-uptake-efflux-and-location-in-a-cell
#6
Anna Janaszewska, Maciej Studzian, Johannes F Petersen, Mario Ficker, Valentina Paolucci, Jørn B Christensen, Donald A Tomalia, Barbara Klajnert-Maculewicz
Traditional amine terminated PAMAM dendrimers may be readily surface engineered by a facile one-pot conversion with dialkyl itaconate esters into 4-carbomethoxypyrrolidone terminated PAMAM (G=0-4) dendrimers. These terminated dendrimers are uniquely characterized by exhibiting blue fluorescence emissions (λexc=370nm, λmaxem=440nm). Thanks to this property they can be directly analyzed by confocal microscopy and flow cytometry without additional fluorescence labeling, treatment of dendrimers with chemicals or adjusting pH...
July 29, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28797837/endosomal-sort-of-signaling-control-the-role-of-escrt-machinery-in-regulation-of-receptor-mediated-signaling-pathways
#7
REVIEW
Ewelina Szymanska, Noga Budick-Harmelin, Marta Miaczynska
The endosomal sorting complexes required for transport (ESCRTs) machinery consists of four protein assemblies (ESCRT-0 to -III subcomplexes) which mediate various processes of membrane remodeling in the cell. In the endocytic pathway, ESCRTs sort cargo destined for degradation into intraluminal vesicles (ILVs) of endosomes. Cargos targeted by ESCRTs include various signaling molecules, mainly internalized cell-surface receptors but also some cytosolic proteins. It is therefore expected that aberrant trafficking caused by ESCRT dysfunction affects different signaling pathways...
August 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28794269/the-fc%C3%AE%C2%B5ri-signaling-cascade-and-integrin-trafficking-converge-at-patterned-ligand-surfaces
#8
Devin L Wakefield, David Holowka, Barbara Baird
We examined the spatial targeting of early and downstream signaling mediated by the IgE receptor (FcεRI) in RBL mast cells utilizing surface-patterned 2,4 dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge-concentrated for DNP-BSA...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28791641/using-percoll-gradient-fractionation-to-study-the-endocytic-trafficking-of-the-egfr
#9
Julie A Gosney, Brian P Ceresa
Scientists have separated subcellular compartments based on differences in their densities by gradient centrifugation for decades. With the proper equipment and thoughtful experimental design, density gradients are a reliable method for enriching various intracellular compartments to assess their protein composition, morphology, or biochemical activity. While variations of this basic technique have been used for separating whole cells, endosomes, synaptic vesicles, and viruses, we have found it especially useful for resolving the compartments of the endocytic pathway...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791639/two-pulse-endosomal-stimulation-of-receptor-tyrosine-kinases-induces-cell-proliferation
#10
Steven Pennock, Sukhmani Billing, Zhixiang Wang, Yi Wang
Signals transduced from ligand-activated receptor tyrosine kinases (RTKs) lead to a diverse array of biological outcomes, such as cell proliferation. Strict regulation of RTK activity is therefore necessary to prevent aberrancies in cell signaling that can lead to diseases such as cancer. RTKs are activated at the plasma membrane (PM) upon ligand binding. Contrary to the initial belief, RTK activity does not terminate immediately following endocytosis, instead RTKs remain active while being trafficked in endosomes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791438/vps52-induces-apoptosis-via-cathepsin-d-in-gastric-cancer
#11
Jian Zhang, Ying Lin, Xichun Hu, Zheng Wu, Weijian Guo
Vacuolar protein sorting (VPS) genes encode a class of proteins involved in vesicular trafficking. Growing evidence suggests that VPS proteins play roles in tumor biology. Vacuolar protein sorting 52 (VPS52) is involved in retrograde transport of endosomes, and its roles in cancers have not been explored. This study investigated the genetic alterations, protein changes, biological role, and molecular mechanism of VPS52 in gastric cancer. Loss of heterozygosity of VPS52 was detected in 52.9% (9/17) of gastric cancer samples...
August 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28775156/the-sharpin-interactome-reveals-a-role-for-sharpin-in-lamellipodium-formation-via-the-arp2-3-complex
#12
Meraj H Khan, Siiri I Salomaa, Guillaume Jacquemet, Umar Butt, Mitro Miihkinen, Takahiro Deguchi, Elena Kremneva, Pekka Lappalainen, Martin J Humphries, Jeroen Pouwels
Sharpin, a multifunctional adaptor protein, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify signalling pathways regulated by Sharpin has not been reported. Here, we present the first 'Sharpin interactome', which identifies a large amount of novel potential Sharpin interactors in addition to several known ones...
August 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28771332/cathepsin-mediated-cleavage-of-peptides-from-peptide-amphiphiles-leads-to-enhanced-intracellular-peptide-accumulation
#13
Handan Acar, Ravand Samaeekia, Matthew R Schnorenberg, Dibyendu K Sasmal, Jun Huang, Matthew V Tirrell, James L LaBelle
Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein-protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide Amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation and PA monomers are internalized via endocytosis...
August 3, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28770472/vacuole-inducing-compounds-that-disrupt-endolysosomal-trafficking-stimulate-production-of-exosomes-by-glioblastoma-cells
#14
Zehui Li, Nneka E Mbah, William A Maltese
Exosomes are produced from mammalian cells when multivesicular endosomes fuse with the plasma membrane, releasing their intralumenal vesicles. In this study we assessed the effects of MOPIPP, a novel indole-based chalcone, and vacuolin-1, a distinct triazine-based compound, on exosome production in cultured glioblastoma and 293T cells. Both compounds promote vacuolization of late endosome compartments and interfere with trafficking of late endosomes to lysosomes, without significant cytotoxicity. The results show that vacuolated cells treated with these compounds release exosomes with morphologies similar to untreated controls...
August 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28768823/manganese-induced-trafficking-and-turnover-of-gpp130-is-mediated-by-sortilin
#15
Swati Venkat, Adam D Linstedt
Elevated, non-toxic doses of manganese (Mn) protect against Shiga toxin-1 induced cell death via down regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi, causes GPP130 to oligomerize/aggregate and the complexes are diverted to lysosomes. In fact, based on experiments using the self-interacting FM domain, it appears generally true that aggregation of a Golgi protein leads to its lysosomal degradation. How such oligomers are selectively sorted out of the Golgi is unknown...
August 2, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28768144/the-c-terminal-domain-of-zdhhc2-contains-distinct-sorting-signals-that-regulate-intracellular-localisation-in-neurons-and-neuroendocrine-cells
#16
Christine Salaun, Louise Ritchie, Jennifer Greaves, Trevor J Bushell, Luke H Chamberlain
The S-acyltransferase zDHHC2 mediates dynamic S-acylation of PSD95 and AKAP79/150, which impacts synaptic targeting of AMPA receptors. zDHHC2 is responsive to synaptic activity and catalyses the increased S-acylation of PSD95 that occurs following action potential blockade or application of ionotropic glutamate receptor antagonists. These treatments have been proposed to increase plasma membrane delivery of zDHHC2 via an endosomal cycling pathway, enhancing substrate accessibility. To generate an improved understanding of zDHHC2 trafficking and how this might be regulated by neuronal activity, we searched for intramolecular signals that regulate enzyme localisation...
July 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28765557/the-voltage-dependent-anion-channels-vdac-of-mycobacterium-avium-phagosome-are-associated-with-bacterial-survival-and-lipid-export-in-macrophages
#17
Lia Danelishvili, Jessica J J Chinison, Tuan Pham, Rashmi Gupta, Luiz E Bermudez
Mycobacterium avium subsp. hominissuis is associated with infection of immunocompromised individuals as well as patients with chronic lung disease. M. avium infects macrophages and actively interfere with the host killing machinery such as apoptosis and autophagy. Bacteria alter the normal endosomal trafficking, prevent the maturation of phagosomes and modify many signaling pathways inside of the macrophage by secreting effector molecules into the cytoplasm. To investigate whether M. avium needs to attach to the internal surface of the vacuole membrane before releasing efferent molecules, vacuole membrane proteins were purified and binding to the surface molecules present in intracellular bacteria was evaluated...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762868/investigating-intracellular-persistence-of-staphylococcus-aureus-within-a-murine-alveolar-macrophage-cell-line
#18
A Lacoma, V Cano, D Moranta, V Regueiro, D Domínguez-Villanueva, M Laabei, M González-Nicolau, V Ausina, C Prat, J A Bengoechea
OBJECTIVE: Staphylococcus aureus is a particularly difficult pathogen to eradicate from the respiratory tract. Previous studies have highlighted the intracellular capacity of S.aureus in a number of phagocytic and non-phagocytic cells. The aim of this study was to define S.aureus interaction within a murine alveolar macrophage cell line. METHODS: Cell line MH-S was infected with Newman strain. Molecular mechanisms involved in phagocytosis were explored. To assess whether S...
August 1, 2017: Virulence
https://www.readbyqxmd.com/read/28759649/the-tetraspanin-cd9-facilitates-mers-coronavirus-entry-by-scaffolding-host-cell-receptors-and-proteases
#19
James T Earnest, Michael P Hantak, Kun Li, Paul B McCray, Stanley Perlman, Tom Gallagher
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28757549/updated-insight-into-the-physiological-and-pathological-roles-of-the-retromer-complex
#20
REVIEW
Yakubu Saddeeq Abubakar, Wenhui Zheng, Stefan Olsson, Jie Zhou
Retromer complexes mediate protein trafficking from the endosomes to the trans-Golgi network (TGN) or through direct recycling to the plasma membrane. In yeast, they consist of a conserved trimer of the cargo selective complex (CSC), Vps26-Vps35-Vps29 and a dimer of sorting nexins (SNXs), Vps5-Vps17. In mammals, the CSC interacts with different kinds of SNX proteins in addition to the mammalian homologues of Vps5 and Vps17, which further diversifies retromer functions. The retromer complex plays important roles in many cellular processes including restriction of invading pathogens...
July 25, 2017: International Journal of Molecular Sciences
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