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Early endosome

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https://www.readbyqxmd.com/read/29158816/dual-targeting-theranostic-system-with-mimicking-apoptosis-to-promote-myocardial-infarction-repair-via-modulation-of-macrophages
#1
Jingli Chen, Jun Yang, Ruiyuan Liu, Chenmeng Qiao, Zhiguo Lu, Yuanjie Shi, Zhanming Fan, Zhenzhong Zhang, Xin Zhang
Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery...
2017: Theranostics
https://www.readbyqxmd.com/read/29158485/cytoplasmic-cleavage-of-dppa3-is-required-for-intracellular-trafficking-and-cleavage-stage-development-in-mice
#2
Seung-Wook Shin, Edgar John Vogt, Maria Jimenez-Movilla, Boris Baibakov, Jurrien Dean
Degradation of maternal proteins by the ubiquitin-proteasome system (UPS) accompanies the maternal-to-zygotic transition. DPPA3/Stella/PGC7, encoded by a maternal effect gene, is present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation. We now report that cytoplasmic DPPA3 is partially cleaved by the ubiquitin-proteasome system and an N-terminus fragment remains in the cytoplasm where it associates with early and re-cycling endosomes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#3
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29152583/inhibition-of-retrograde-transport-limits-polyomavirus-infection-in-vivo
#4
Saumya Maru, Ge Jin, Dhimant Desai, Shantu Amin, Shwetank, Matthew D Lauver, Aron E Lukacher
Polyomaviruses (PyVs) silently infect most humans, but they can cause life-threatening diseases in immunocompromised individuals. The JC polyomavirus (JCPyV) induces progressive multifocal leukoencephalopathy, a severe demyelinating disease in multiple sclerosis patients receiving immunomodulatory therapy, and BK polyomavirus (BKPyV)-associated nephropathy is a major cause of kidney allograft failure. No effective anti-PyV agents are available. Several compounds have been reported to possess anti-PyV activity in vitro, but none have shown efficacy in clinical trials...
November 2017: MSphere
https://www.readbyqxmd.com/read/29150640/early-endosome-motility-mediates-%C3%AE-amylase-production-and-cell-differentiation-in-aspergillus-oryzae
#5
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/29142761/aeromonas-hydrophila-utilizes-tlr4-topology-for-synchronous-activation-of-myd88-and-trif-to-orchestrate-anti-inflammatory-responses-in-zebrafish
#6
Nidhi Srivastava, Asha Shelly, Manmohan Kumar, Archana Pant, Bhabatosh Das, Tanmay Majumdar, Shibnath Mazumder
Toll-like receptor 4 (TLR4) plays a critical role in host immunity against Gram-negative bacteria. It transduces signals through two distinct TIR-domain-containing adaptors, MyD88 and TRIF, which function at the plasma membrane and endosomes, respectively. Using zebrafish Aeromonas hydrophila infection model, we demonstrate that synchronization of MyD88 and TRIF dependent pathways is critical for determining the fate of infection. Zebrafish were infected with A. hydrophila, and bacterial recovery studies suggested its effective persistence inside the host...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#7
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29141870/ig%C3%AE-ubiquitination-activates-pi3k-signals-required-for-endosomal-sorting
#8
Margaret Veselits, Azusa Tanaka, Yaoqing Chen, Keith Hamel, Malay Mandal, Matheswaran Kandasamy, Balaji Manicassamy, Shannon K O'Neill, Patrick Wilson, Roger Sciammas, Marcus R Clark
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC)...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#9
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29138439/abma-a-small-molecule-that-inhibits-intracellular-toxins-and-pathogens-by-interfering-with-late-endosomal-compartments
#10
Yu Wu, Valérie Pons, Amélie Goudet, Laetitia Panigai, Annette Fischer, Jo-Ana Herweg, Sabrina Kali, Robert A Davey, Jérôme Laporte, Céline Bouclier, Rahima Yousfi, Céline Aubenque, Goulven Merer, Emilie Gobbo, Roman Lopez, Cynthia Gillet, Sandrine Cojean, Michel R Popoff, Pascal Clayette, Roger Le Grand, Claire Boulogne, Noël Tordo, Emmanuel Lemichez, Philippe M Loiseau, Thomas Rudel, Didier Sauvaire, Jean-Christophe Cintrat, Daniel Gillet, Julien Barbier
Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133347/analysis-of-the-human-mucosal-response-to-cholera-reveals-sustained-activation-of-innate-immune-signaling-pathways
#11
Daniel L Bourque, Taufiqur Rahman Bhuiyan, Diane P Genereux, Rasheduzzaman Rashu, Crystal N Ellis, Fahima Chowdhury, Ashraful I Khan, Nur Haq Alam, Anik Paul Lazina Hossain, Leslie M Mayo-Smith, Richelle C Charles, Ana A Weil, Regina C LaRocque, Stephen B Calderwood, Edward T Ryan, Elinor K Karlsson, Firdausi Qadri, Jason B Harris
To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29128415/the-p38-mitogen-activated-protein-kinase-regulates-%C3%AE-amyloid-protein-internalization-through-the-%C3%AE-7-nicotinic-acetylcholine-receptor-in-mouse-brain
#12
Kai-Ge Ma, Jia Lv, Wei-Na Yang, Ke-Wei Chang, Xiao-Dan Hu, Li-Li Shi, Wan-Ying Zhai, Hang-Fan Zong, Yi-Hua Qian
Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. Intracellular β-amyloid protein (Aβ) is an early event in AD. It induces the formation of amyloid plaques and neuron damage. The α7 nicotinic acetylcholine receptor (α7nAChR) has been suggested to play an important role in Aβ caused cognition. It has high affinity with Aβ and could mediate Aβ internalization in vitro. However, whether in mouse brain the p38 MAPK signaling pathway is involved in the regulation of the α7nAChR mediated Aβ internalization and their role in mitochondria remains little known...
November 9, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29128232/liposome-based-immunity-inducing-systems-for-cancer-immunotherapy
#13
REVIEW
Eiji Yuba
Cancer immunotherapy has gained much attention for next-generation cancer treatment. To conduct cancer immunotherapy, efficient antigen delivery systems must be able to deliver an antigen selectively to antigen-presenting cells, release it at suitable sites for induction of cross-presentation, and simultaneously induce activation of immunocompetent cells. Liposomes are a candidate for use as such multifunctional antigen delivery carriers because of their capability for easy functionalization. This review describes the rational design of liposome-based antigen delivery systems...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29123089/tsg101-chaperone-function-revealed-by-hiv-1-assembly-inhibitors
#14
Madeleine Strickland, Lorna S Ehrlich, Susan Watanabe, Mahfuz Khan, Marie-Paule Strub, Chi-Hao Luan, Michael D Powell, Jonathan Leis, Nico Tjandra, Carol A Carter
HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29117566/cytosolic-recognition-of-rna-drives-the-immune-response-to-heterologous-erythrocytes
#15
Claudia Loetsch, Joanna Warren, Adrienne Laskowski, Rodrigo Vazquez-Lombardi, Christoph Jandl, David B Langley, Daniel Christ, David R Thorburn, David K Ryugo, Jonathan Sprent, Marcel Batten, Cecile King
The archetypal T cell-dependent antigen is sheep red blood cells (SRBCs), which have defined much of what we know about humoral immunity. Early studies using solubilized or sonicated SRBCs argued that the intact structure of SRBCs was important for optimal antibody responses. However, the reason for the requirement of intact SRBCs for the response to polyvalent protein antigen remained unknown. Here, we report that the immune response to SRBCs is driven by cytosolic recognition of SRBC RNA through the RIG-I-like receptor (RLR)-mitochondrial anti-viral signaling adaptor (MAVS) pathway...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29117102/mechanisms-of-entry-and-endosomal-pathway-of-african-swine-fever-virus
#16
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/29108990/laminin-1-induces-endocytosis-of-67kda-laminin-receptor-and-protects-neuroscreen-1-cells-against-death-induced-by-serum-withdrawal
#17
Rayudu Gopalakrishna, Usha Gundimeda, Sarah Zhou, Helena Bui, Andrew Davis, Thomas McNeill, William Mack
Although the function of laminin in the basement membrane is known, the function of soluble "neuronal" laminin is unknown. Since laminin is neuroprotective, we determined whether the soluble laminin-1 induces signaling for neuroprotection via its 67KDa laminin-1 receptor (67LR). Treatment of Neuroscreen-1 (NS-1) cells with laminin-1 or YIGSR peptide, which corresponds to a sequence in laminin-1 β1 chain that binds to 67LR, induced a decrease in the cell-surface expression of 67LR and caused its internalization...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29099266/calpain2-mediates-rab5-driven-focal-adhesion-disassembly-and-cell-migration
#18
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/29097235/unc93b1-is-essential-for-cytokine-activation-of-five-pamps-in-the-orange-spotted-grouper-epinephelus-coioides
#19
Yaosi Liang, Yu Wang, Liangge He, Jianan He, Wan Peng, Libin Zhou, Yong Zhang, Haifa Zhang, Herong Shi, Haoran Lin, Danqi Lu
Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 (unc93b1), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco...
October 31, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29093485/dynamic-fingerprinting-of-sub-cellular-nanostructures-by-image-mean-square-displacement-analysis
#20
Luca Digiacomo, Francesca D'Autilia, William Durso, Paolo Maria Tentori, Giulio Caracciolo, Francesco Cardarelli
Here we provide demonstration that image mean square displacement (iMSD) analysis is a fast and robust platform to address living matter dynamic organization at the level of sub-cellular nanostructures (e.g. endocytic vesicles, early/late endosomes, lysosomes), with no a-priori knowledge of the system, and no need to extract single trajectories. From each iMSD, a unique triplet of average parameters (namely: diffusivity, anomalous coefficient, size) are extracted and represented in a 3D parametric space, where clustering of single-cell points readily defines the structure "dynamic fingerprint", at the whole-cell-population level...
November 1, 2017: Scientific Reports
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