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Cellular trafficking

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https://www.readbyqxmd.com/read/29452206/snx10-mediates-alcohol-induced-liver-injury-and-steatosis-via-regulating-chaperone-mediated-autophagy-activation
#1
Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
BACKGROUND & AIMS: Alcoholic liver disease is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX) 10 has a regulatory function in endo-lysosomal trafficking and stabilization. Here we investigated the roles of SNX10 in CMA activation and the pathogenesis of alcohol-induced liver injury and steatosis...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29451726/single-organelle-dynamics-linked-to-3d-structure-by-correlative-live-cell-3d-electron-microscopy
#2
Job Fermie, Nalan Liv, Corlinda Ten Brink, Elly G van Donselaar, Wally H Müller, Nicole L Schieber, Yannick Schwab, Hans C Gerritsen, Judith Klumperman
Live-cell correlative light-electron microscopy (live-cell-CLEM) integrates live movies with the corresponding EM image, but a major challenge is to relate the dynamic characteristics of single organelles to their 3D ultrastructure. Here we introduce focused ion beam scanning electron microscopy (FIB-SEM) in a modular live-cell CLEM pipeline for single organelle CLEM. We transfected cells with LAMP-1-GFP, analyzed the dynamics of individual GFP-positive spots, and correlated these to their corresponding fine-architecture and immediate cellular environment...
February 16, 2018: Traffic
https://www.readbyqxmd.com/read/29451723/clickable-polyamine-derivatives-as-chemical-probes-for-the-polyamine-transport-system
#3
Roeland Vanhoutte, Jan Pascal Kahler, Shaun Martin, Sarah van Veen, Steven Verhelst
Polyamines are essential for cell growth and differentiation, but their trafficking by the polyamine transport system is not fully understood. In this paper, we describe the synthesis of several azido-derivatized polyamines for easy conjugation by click chemistry. Attachment of a BODIPY-dye gave fluorescent polyamine probes, which were tested in cell culture. The linear probe series showed superior cellular uptake compared with the probes where the dye was attached to a branch on one of the central amines. Interestingly, the linear probes accumulated rapidly in cancer cells (MCF-7), but not in non-tumorigenic cells (MCF-10A)...
February 16, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29451682/metabolic-regulation-of-leukocyte-motility-and-migration
#4
REVIEW
Federica M Marelli-Berg, Maryam Jangani
Dynamic reorganization of the cytoskeleton is essential for numerous cellular processes including leukocyte migration. This process presents a substantial bioenergetic challenge to migrating cells as actin polymerization is dependent on ATP hydrolysis. Hence, migrating cells must increase ATP production to meet the increased metabolic demands of cytoskeletal reorganization. Despite this long-standing evidence, the metabolic regulation of leukocyte motility and trafficking has only recently begun to be investigated...
February 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#5
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29447473/impact-of-micronutrients-on-the-immune-response-of-animals
#6
Allen D Smith, Kiran S Panickar, Joseph F Urban, Harry D Dawson
Vitamins and minerals (micronutrients) play an important role in regulating and shaping an immune response. Deficiencies generally result in inadequate or dysregulated cellular activity and cytokine expression, thereby affecting the immune response. Decreased levels of natural killer, granulocyte, and phagocytic cell activity and T and B cell proliferation and trafficking are associated with inadequate levels of micronutrients, as well as increased susceptibility to various adverse health conditions, including inflammatory disorders, infection, and altered vaccine efficacy...
February 15, 2018: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/29444946/karyopherin-alpha6-is-required-for-the-replication-of-porcine-reproductive-and-respiratory-syndrome-virus-and-zika-virus
#7
Liping Yang, Rong Wang, Shixing Yang, Zexu Ma, Shaoli Lin, Yuchen Nan, Qisheng Li, Qiyi Tang, Yan-Jin Zhang
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating nucleocytoplasmic translocation of proteins through the NPC. In this study, we discovered that karyopherin alpha6 (KPNA6, also known as importin alpha7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29444827/site-specific-polyubiquitination-differentially-regulates-parathyroid-hormone-receptor-initiated-mapk-signaling-and-cell-proliferation
#8
Qiangmin Zhang, Kunhong Xiao, Hongda Liu, Lei Song, Jennifer C McGarvey, W Bruce Sneddon, Alessandro Bisello, Peter A Friedman
G protein-coupled receptor (GPCR) signaling and trafficking are essential for cellular function and regulated by phosphorylation, β-arrestin, and ubiquitination. The GPCR parathyroid hormone receptor (PTHR) exhibits time-dependent reversible ubiquitination. The exact ubiquitination sites in PTHR are unknown, but extend upstream of its intracellular tail. Here, using tandem MS, we identified Lys-388 in the third loop and Lys-484 in the C-terminal tail as primary ubiquitination sites in PTHR. We found that PTHR ubiquitination requires β-arrestin and does not display a preference for β-arrestin1 or 2...
February 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29439330/hypoxia-induced-signaling-activation-in-neurodegenerative-diseases-targets-for-new-therapeutic-strategies
#9
Niraj Kumar Jha, Saurabh Kumar Jha, Renu Sharma, Dhiraj Kumar, Rashmi K Ambasta, Pravir Kumar
For the maintenance of cellular homeostasis and energy metabolism, an uninterrupted supply of oxygen (O2) is routinely required in the brain. However, under the impaired level of O2 (hypoxia) or reduced blood flow (ischemia), the tissues are not sufficiently oxygenated, which triggers disruption of cellular homeostasis in the brain. Hypoxia is known to have a notable effect on controlling the expression of proteins involved in a broad range of biological processes varying from energy metabolism, erythropoiesis, angiogenesis, neurogenesis to mitochondrial trafficking and autophagy, thus facilitating neuronal cells to endure in deprived O2...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29438268/endocytosis-of-red-blood-cell-microparticles-by-pulmonary-endothelial-cells-is-mediated-by-rab5
#10
Young Kim, William A Abplanalp, Andrew D Jung, Rebecca M Schuster, Alex B Lentsch, Erich Gulbins, Charles C Caldwell, Timothy A Pritts
Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6...
March 2018: Shock
https://www.readbyqxmd.com/read/29437871/gut-microbiota-modulate-t-cell-trafficking-into-human-colorectal-cancer
#11
Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues...
February 6, 2018: Gut
https://www.readbyqxmd.com/read/29437530/endosomal-escape-of-asos-internalized-by-stabilin-receptors-is-regulated-by-rab5c-and-eea1-during-endosomal-maturation
#12
Colton M Miller, W Brad Wan, Punit P Seth, Edward N Harris
Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, which enhances ASO interactions with plasma, cell surface, and intracellular proteins. This facilitates ASO distribution to peripheral tissues and also promotes cellular uptake after injection into animals. Previous work identified that Stabilin receptors specifically internalize PS-ASOs in the sinusoidal endothelial cells of the liver and the spleen...
February 13, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29437282/phagocytosis-of-antibody-opsonized-tumor-cells-leads-to-the-formation-of-a-discrete-vacuolar-compartment-in-macrophages
#13
Ramraj Velmurugan, Sreevidhya Ramakrishnan, Mingin Kim, Raimund J Ober, E Sally Ward
Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome...
February 13, 2018: Traffic
https://www.readbyqxmd.com/read/29436995/bacterial-luciferase-gene-cassette-as-a-real-time-bioreporter-for-infection-model-and-drug-evaluation
#14
Xiwen Wang, Hang Chi, Bo Zhou, Wenliang Li, Zhiping Li, Zhiping Xia
The bacterial luciferase gene cassette (lux) is an ideal bioreporter for real-time monitoring of the dynamics of bacteria because it is a fully autonomous, substrate-free bioluminescent reporter system available in a prokaryotic or eukaryotic host background. The lux operon is emerging as a powerful bioreporter for the study of a wide range of biological processes such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis and cancer treatment...
February 13, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29436197/the-role-of-serotonin-in-ventricular-repolarization-in-pregnant-mice
#15
Shanyu Cui, Hyewon Park, Hyelim Park, Dasom Mun, Seung Hyun Lee, Hyoeun Kim, Nuri Yun, Hail Kim, Michael Kim, Hui Nam Pak, Moon Hyoung Lee, Boyoung Joung
PURPOSE: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. MATERIALS AND METHODS: We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP)...
March 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29435651/the-neutrophil-one-cell-on-many-missions-or-many-cells-with-different-agendas
#16
REVIEW
Gustaf Christoffersson, Mia Phillipson
The unique role of neutrophils in host defense is not only based on their abilities to kill bacteria but is also due to their abundance in circulation and their ability to quickly migrate and accumulate in great numbers at afflicted sites. The high number of circulating neutrophils is the result of regulated release of new neutrophils from bone marrow as well as from marginated pools to balance their recruitment to tissue. Marginated pools, such as the spleen and lung, have previously been attributed to passively delay neutrophil transit time due to their large capillary network, but recent reports demonstrate that they are comprised of neutrophils with specific functions...
February 12, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29433309/nls-cholic-acid-conjugation-to-il-5r%C3%AE-specific-antibody-improves-cellular-accumulation-and-in-vivo-tumor-targeting-properties-in-a-bladder-cancer-model
#17
Michel Paquette, Simon Beaudoin, Mylene-Annie Tremblay, Steve Jean, Angel F Lopez, Roger Lecomte, Brigitte Guérin, M'hamed Bentourkia, Robert Sabbagh, Jeffrey V Leyton
Receptor-mediated internalization followed by trafficking and degradation of antibody-conjugates (ACs) via the endosomal-lysosomal pathway is the major mechanism for delivering molecular payloads inside target tumor cells. Although, a mainstay for delivering payloads with clinically approved ACs in cancer treatment and imaging, tumor cells are often able to decrease intracellular payload concentrations and thereby reduce the effectiveness of the desired application. Thus, increasing payload intracellular accumulation has become a focus of attention for designing next-generation ACs...
February 13, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29427087/neuroinflammation-alters-integrative-properties-of-rat-hippocampal-pyramidal-cells
#18
Federica Frigerio, Corey Flynn, Ye Han, Kyle Lyman, Joaquin N Lugo, Teresa Ravizza, Antoine Ghestem, Julika Pitsch, Albert Becker, Anne E Anderson, Annamaria Vezzani, Dane Chetkovich, Christophe Bernard
Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4...
February 9, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29426865/the-wdr11-complex-facilitates-the-tethering-of-ap-1-derived-vesicles
#19
Paloma Navarro Negredo, James R Edgar, Paul T Manna, Robin Antrobus, Margaret S Robinson
Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that WDR11 forms a stable complex with two other proteins, which localises to the TGN region and does not appear to be associated with AP-1, suggesting it may act downstream from budding...
February 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29426014/network-analysis-of-ube3a-e6ap-associated-proteins-provides-connections-to-several-distinct-cellular-processes
#20
Gustavo Martínez-Noël, Katja Luck, Simone Kühnle, Alice Desbuleux, Patricia Szajner, Jeffrey T Galligan, Diana Rodriguez, Leon Zheng, Kathleen Boyland, Flavian Leclere, Quan Zhong, David E Hill, Marc Vidal, Peter M Howley
Perturbations in activity and dosage of the UBE3A ubiquitin-ligase have been linked to Angelman Syndrome and autism spectrum disorders. UBE3A was initially identified as the cellular protein hijacked by the human papillomavirus E6 protein to mediate the ubiquitylation of p53, a function critical to the oncogenic potential of these viruses. Although a number of substrates have been identified, the normal cellular functions and pathways affected by UBE3A are largely unknown. Previously we showed that UBE3A associates with HERC2, NEURL4, and MAPK6/ERK3 in a high molecular weight complex of unknown function that we refer to as the HUN complex (HERC2, UBE3A, and NEURL4)...
February 6, 2018: Journal of Molecular Biology
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