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https://www.readbyqxmd.com/read/28199124/tempo-spatial-activation-of-sequential-quadruple-stimuli-for-high-gene-expression-of-polymeric-gene-nanocomplexes
#1
Hana Cho, Young-Woo Cho, Sun-Woong Kang, Mi-Kyoung Kwak, Kang Moo Huh, You Han Bae, Han Chang Kang
The clinical application of intracellular gene delivery via nanosized carriers is hindered by intracellular multistep barriers that limit high levels of gene expression. To solve these issues, four different intracellular or external stimuli that can efficiently activate a gene carrier, a gene, or a photosensitizer (pheophorbide A [PhA]) were assessed in this study. The designed nanosized polymeric gene complexes were composed of PhA-loaded thiol-degradable polycation (PhA@RPC) and cytomegalovirus (CMV) promoter-equipped pDNA...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28191740/insulin-dependent-cytoplasmic-distribution-of-rab4a-in-mouse-adipocytes-is-inhibited-by-interleukin-6-8-and-15
#2
Maciej Błaszczyk, Małgorzata Gajewska, Mart Milewska, Katarzyna Grzelkowska-Kowalczyk
The purpose of the study was to examine the effect of interleukins, IL-6, IL-8 and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, i...
February 13, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28188999/the-small-gtpase-arf6-regulates-sea-urchin-morphogenesis
#3
Nadezda A Stepicheva, Megan Dumas, Priscilla Kobi, Julie G Donaldson, Jia L Song
The small GTPase Arf6 is a conserved protein that is expressed in all metazoans. Arf6 remodels cytoskeletal actin and mediates membrane protein trafficking between the plasma membrane in its active form and endosomal compartments in its inactive form. While a rich knowledge exists for the cellular functions of Arf6, relatively little is known about its physiological role in development. This study examines the function of Arf6 in mediating cellular morphogenesis in early development. We dissect the function of Arf6 with a loss-of-function morpholino and constitutively active Arf6-Q67L construct...
February 2, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28176461/high-resolution-localization-of-rab5-eea1-and-nectin-3-to-tubulobulbar-complexes-in-the-rat-testis
#4
Arlo Adams, A Wayne Vogl
Tubulobulbar complexes are clathrin/actin-based structures that internalize intercellular junctions in the testis. They resemble coated pits with extremely long necks that are cuffed by dendritic actin networks. As the structures mature, a swollen region or bulb develops near the end of each complex. The bulbs lack actin cuffs and are closely associated with cisternae of endoplasmic reticulum. The bulbs expand and are internalized and enter endocytic compartments of the Sertoli cell. Previous immunofluorescence studies have demonstrated that markers for early endosomes (Rab5 and EEA1) are associated with tubulobulbar complexes and are localized at or near the ends of the structures...
February 8, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28174296/ncs1-regulates-ca2-dependent-focal-exocytosis-of-golgi-derived-vesicles-to-help-phagocytic-uptake-in-macrophages
#5
Nimi Vashi, Syed Bilal Ahmad Andrabi, Swapnil Ghanwat, Mrutyunjay Suar, Dhiraj Kumar
During phagocytic uptake by macrophages, role of Golgi apparatus was previously ruled out. Notably all such reports were limited to Fcγ-receptor mediated phagocytosis. Here we unravel a highly devolved mechanism for recruitment of Golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos except IgG-coated ones. We report recruitment of Mannosidase-II positive Golgi-derived vesicles during uptake of diverse targets including latex beads, E. coli, Salmonella Typhimurium and Mycobacterium tuberculosis in human and mouse macrophages...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28166442/exosomes-in-cancer-theranostic-diamonds-in-the-rough
#6
Marine Cordonnier, Gaëtan Chanteloup, Nicolas Isambert, Renaud Seigneuric, Pierre Fumoleau, Carmen Garrido, Jessica Gobbo
During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers...
February 6, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28159908/regulation-of-synaptic-a%C3%AE-generation-through-bace1-retrograde-transport-in-a-mouse-model-of-alzheimer-s-disease
#7
Xuan Ye, Tuancheng Feng, Prasad Tammineni, Qing Chang, Yu Young Jeong, David J Margolis, Huaibin Cai, Alexander Kusnecov, Qian Cai
: β-amyloid (Aβ) peptides play a key role in synaptic damage and memory deficits in the early pathogenesis of Alzheimer's disease (AD). Abnormal accumulation of Aβ at nerve terminals leads to synaptic pathology and ultimately to neurodegeneration. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for Aβ generation. However, the mechanisms regulating BACE1 distribution in axons and β cleavage of APP at synapses remain largely unknown...
February 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28158302/host-cell-interactions-of-outer-membrane-vesicle-associated-virulence-factors-of-enterohemorrhagic-escherichia-coli-o157-intracellular-delivery-trafficking-and-mechanisms-of-cell-injury
#8
Martina Bielaszewska, Christian Rüter, Andreas Bauwens, Lilo Greune, Kevin-André Jarosch, Daniel Steil, Wenlan Zhang, Xiaohua He, Roland Lloubes, Angelika Fruth, Kwang Sik Kim, M Alexander Schmidt, Ulrich Dobrindt, Alexander Mellmann, Helge Karch
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28157837/a-novel-surfactant-protein-c-mutation-resulting-in-aberrant-protein-processing-and-altered-subcellular-localization-causes-infantile-interstitial-lung-disease
#9
Da Hong, Yuanyuan Qi, Jing Liu, Huijun Wang, Libo Wang, Liling Qian
BACKGROUND: Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to report a novel SFTPC mutation and evaluate the effect of this mutant on protein synthesis and processing. METHODS: Genomic DNA was extracted from whole blood of a Chinese infant with ILD and candidate genes associated with ILD were sequenced by next-generation sequencing. Subclones of wild-type and mutant SFTPC were transiently transfected into A549 cells...
February 3, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28137951/correction-for-bloc-1-is-required-for-cargo-specific-sorting-from-vacuolar-early-endosomes-toward-lysosome-related-organelles
#10
(no author information available yet)
No abstract text is available yet for this article.
February 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28134239/a-rab5-endosomal-pathway-mediates-parkin-dependent-mitochondrial-clearance
#11
Babette C Hammerling, Rita H Najor, Melissa Q Cortez, Sarah E Shires, Leonardo J Leon, Eileen R Gonzalez, Daniela Boassa, Sébastien Phan, Andrea Thor, Rebecca E Jimenez, Hong Li, Richard N Kitsis, Gerald W Dorn Ii, Junichi Sadoshima, Mark H Ellisman, Åsa B Gustafsson
Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28130443/na-h-exchanger-9-regulates-iron-mobilization-at-the-blood-brain-barrier-in-response-to-iron-starvation
#12
Rami Beydoun, Mohamed A Hamood, Daniela M Gomez Zubeita, Kalyan C Kondapalli
Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain-iron status information via paracrine signals from ensheathing astrocytes...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28119475/%C3%AE-defensin-hd5-inhibits-human-papillomavirus-16-infection-via-capsid-stabilization-and-redirection-to-the-lysosome
#13
Mayim E Wiens, Jason G Smith
: α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5) blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV) infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition...
January 24, 2017: MBio
https://www.readbyqxmd.com/read/28119397/misdirection-of-endosomal-trafficking-mediated-by-herpes-simplex-virus-encoded-glycoprotein-b
#14
Naima Niazy, Sebastian Temme, Derya Bocuk, Carmen Giesen, Angelika König, Nadine Temme, Angelique Ziegfeld, Tone F Gregers, Oddmund Bakke, Thorsten Lang, Anna M Eis-Hübinger, Norbert Koch
Herpes simplex virus (HSV)-encoded glycoprotein B (gB) is the most abundant protein in the viral envelope and promotes fusion of the virus with the cellular membrane. In the present study, we found that gB impacts on the major histocompatibility complex (MHC)-II pathway of antigen presentation by fostering homotypic fusion of early endosomes and trapping MHC-II molecules in these altered endosomes. By using an overexpression approach, we demonstrated that transient expression of gB induces giant vesicles of early endosomal origin, which contained Rab5, early endosomal antigen 1 (EEA1), large amounts of MHC-II molecules [human leukocyte antigen (HLA)-DR, and HLA-DM] but no CD63...
January 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28117704/above-and-beyond-c5a-receptor-targeting-by-staphylococcal-leucotoxins-retrograde-transport-of-panton-valentine-leucocidin-and-%C3%AE-hemolysin
#15
Gaëlle Zimmermann-Meisse, Gilles Prévost, Emmanuel Jover
Various membrane receptors associated with the innate immune response have recently been identified as mediators of the cellular action of Staphylococcus aureus leucotoxins. Two of these, the Panton-Valentine leucotoxin LukS-PV/LukF-PV and the γ-hemolysin HlgC/HlgB, bind the C5a complement-derived peptide receptor. These leucotoxins utilize the receptor to induce intracellular Ca(2+) release from internal stores, other than those activated by C5a. The two leucotoxins are internalized with the phosphorylated receptor, but it is unknown whether they divert retrograde transport of the receptor or follow another pathway...
January 20, 2017: Toxins
https://www.readbyqxmd.com/read/28112392/intracellular-transcytosis-of-albumin-in-glomerular-endothelial-cells-after-endocytosis-through-caveolae
#16
Takahito Moriyama, Kayo Sasaki, Kazunori Karasawa, Keiko Uchida, Kosaku Nitta
BACKGROUND/AIMS: We previously described albumin endocytosis through caveolae in human renal glomerular endothelial cells (HRGECs). This suggested a new albumin transcytosis pathway, in addition to the fenestral pathway. As a next step, we investigated albumin transcytosis in HRGECs after caveolar endocytosis. METHODS AND RESULTS: HRGECs were incubated with Alexa Fluor 488-labeled bovine serum albumin from 0 to 360 minutes. Next, markers for endosomes, endoplasmic reticulum (ER), golgi apparatus (GA), lysosomes and proteasomes and Fc receptors, microtubules and actin were monitored by immunofluorescence...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28108508/two-pore-channel-function-is-crucial-for-migration-of-invasive-cancer-cells
#17
Ong Nam Phuong Nguyen, Christian Grimm, Lina S Schneider, Yu-Kai Chao, Carina Atzberger, Karin Bartel, Anna Watermann, Melanie Ulrich, Doris Mayr, Christian Wahl-Schott, Martin Biel, Angelika M Vollmar
Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2-sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro. Silencing or pharmacological inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#18
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28077878/pla2g16-represents-a-switch-between-entry-and-clearance-of-picornaviridae
#19
Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J M van Kuppeveld, Anastassis Perrakis, Jan E Carette, Thijn R Brummelkamp
Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#20
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
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