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Macropinocytosis

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https://www.readbyqxmd.com/read/28431576/enhanced-neuroinvasion-by-smaller-soluble-prions
#1
Cyrus Bett, Jessica Lawrence, Timothy D Kurt, Christina Orru, Patricia Aguilar-Calvo, Anthony E Kincaid, Witold K Surewicz, Byron Caughey, Chengbiao Wu, Christina J Sigurdson
Infectious prion aggregates can propagate from extraneural sites into the brain with remarkable efficiency, likely transported via peripheral nerves. Yet not all prions spread into the brain, and the physical properties of a prion that is capable of transit within neurons remain unclear. We hypothesized that small, diffusible aggregates spread into the CNS via peripheral nerves. Here we used a structurally diverse panel of prion strains to analyze how the prion conformation impacts transit into the brain. Two prion strains form fibrils visible ultrastructurally in the brain in situ, whereas three strains form diffuse, subfibrillar prion deposits and no visible fibrils...
April 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28431548/water-pipe-smoke-condensate-increases-the-internalization-of-mycobacterium-bovis-of-type-ii-alveolar-epithelial-cells-a549
#2
Esmaeil Mortaz, Shamila D Alipoor, Masoud Movassaghi, Mohammad Varahram, Jahangir Ghorbani, Gert Folkerts, Johan Garssen, Ian M Adcock
BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection...
April 21, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#3
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28416685/snat7-is-the-primary-lysosomal-glutamine-exporter-required-for-extracellular-protein-dependent-growth-of-cancer-cells
#4
Quentin Verdon, Marielle Boonen, Christopher Ribes, Michel Jadot, Bruno Gasnier, Corinne Sagné
Lysosomes degrade cellular components sequestered by autophagy or extracellular material internalized by endocytosis and phagocytosis. The macromolecule building blocks released by lysosomal hydrolysis are then exported to the cytosol by lysosomal transporters, which remain undercharacterized. In this study, we designed an in situ assay of lysosomal amino acid export based on the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis that detects lysosomal storage. This assay was used to screen candidate lysosomal transporters, leading to the identification of sodium-coupled neutral amino acid transporter 7 (SNAT7), encoded by the SLC38A7 gene, as a lysosomal transporter highly selective for glutamine and asparagine...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28402214/eyeing-autophagy-and-macropinocytosis-in-the-corneal-limbal-epithelia
#5
Han Peng, Jong Kook Park, Robert M Lavker
Macroautophagy/autophagy is vital for cellular homeostasis and helps cells respond to various stress situations. Macropinocytosis enables cells to nonselectively engulf and take up large volumes of fluid and is known to supply amino acids to cells. The stem cell-enriched limbal epithelium has the machinery necessary to carry out both autophagy and macropinocytosis; however, both processes are relatively understudied in this tissue. We have demonstrated that these processes are linked via MIR103-MIR107, a microRNA family that is limbal epithelial-preferred...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28391090/fast-and-ultrafast-endocytosis
#6
REVIEW
Shigeki Watanabe, Emmanuel Boucrot
Clathrin-mediated endocytosis (CME) is the main endocytic pathway supporting housekeeping functions in cells. However, CME may be too slow to internalize proteins from the cell surface during certain physiological processes such as reaction to stress hormones ('fight-or-flight' reaction), chemotaxis or compensatory endocytosis following exocytosis of synaptic vesicles or hormone-containing vesicles. These processes take place on a millisecond to second timescale and thus require very rapid cellular reaction to prevent overstimulation or exhaustion of the response...
April 5, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28389565/akt3-kinase-suppresses-pinocytosis-of-low-density-lipoprotein-by-macrophages-via-novel-wnk-sgk1-cdc42-pathway
#7
Liang Ding, Lifang Zhang, Michael Kim, Tatiana Byzova, Eugene Podrez
Fluid-phase pinocytosis of Low-density lipoprotein (LDL) by macrophages is regarded as a novel promising target to reduce macrophage cholesterol accumulation in atherosclerotic lesions. The mechanisms of regulation of fluid-phase pinocytosis in macrophages and specifically the role of Akt kinases are poorly understood. We have previously found that increased lipoprotein uptake via the receptor independent process in Akt3 kinase deficient macrophages contributes to increased atherosclerosis in Akt3-/- mice. The mechanism by which Akt3 deficiency promotes lipoprotein uptake in macrophages is unknown...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28368306/icam-1-binding-rhinoviruses-enter-hela-cells-via-multiple-pathways-and-travel-to-distinct-intracellular-compartments-for-uncoating
#8
Haleh Ganjian, Christin Zietz, Diana Mechtcheriakova, Dieter Blaas, Renate Fuchs
Of the more than 150 human rhinovirus (RV) serotypes, 89 utilize intercellular adhesion molecule-1 (ICAM-1) for cell entry. These belong either to species A or B. We recently demonstrated that RV-B14 and RV-A89, despite binding this same receptor, are routed into distinct endosomal compartments for release of their RNA into the cytosol. To gain insight into the underlying mechanism we now comparatively investigate the port of entry, temperature-dependence of uncoating, and intracellular routing of RV-B3, RV-B14, RV-A16, and RV-A89 in HeLa cells...
April 1, 2017: Viruses
https://www.readbyqxmd.com/read/28347807/retinal-gene-delivery-enhancement-by-lycopene-incorporation-into-cationic-niosomes-based-on-dotma-and-polysorbate-60
#9
Mohamed Mashal, Noha Attia, Gustavo Puras, Gema Martínez-Navarrete, Eduardo Fernández, Jose Luis Pedraz
The present study aimed to evaluate the incorporation of the natural lipid lycopene into niosome formulations based on cationic lipid DOTMA and polysorbate 60 non-ionic surfactant to analyze the potential application of this novel formulation to deliver genetic material into the rat retina. Both niosomes with and without lycopene were prepared by the reverse phase evaporation method and physicochemically characterized in terms of size, zeta potential, polydispersity index and capacity to condense, release and protect the DNA against enzymatic digestion...
March 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28323115/gene-transfection-efficiency-into-dendritic-cells-is-influenced-by-the-size-of-cationic-liposomes-dna-complexes
#10
Yoshikazu Inoh, Mie Nagai, Kayo Matsushita, Mamoru Nakanishi, Tadahide Furuno
Cationic liposomes have attracted recent attention as DNA vaccine carriers that can target dendritic cells (DCs). In general, cationic liposome/DNA complexes (lipoplexes) are taken up by various cells via clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis, or phagocytosis, with the mode of endocytosis determining further intracellular trafficking pathways. Moreover, the physicochemical properties of cationic lipoplexes, including lipid composition, shape, size, and charge, influence transfection efficiency, affecting uptake and subsequent intracellular pathways...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28317223/cancer-with-low-cathepsin-d-levels-is-susceptible-to-v-atpase-inhibition
#11
Satoshi Kitazawa, Satoru Nishizawa, Hideyuki Nakagawa, Masaaki Funata, Kazuho Nishimura, Tomoyoshi Soga, Takahito Hara
Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anti-cancer drugs has not been realized, possibly owing to their high toxicity in humans. V-ATPase inhibition may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity...
March 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28287688/light-induced-translocation-of-a-conjugated-polyelectrolyte-in-cells-from-fluorescent-probe-to-anticancer-agent
#12
Pan Wu, Naihan Xu, Chunyan Tan, Lei Liu, Ying Tan, Zhifang Chen, Yuyang Jiang
Dual-functional probes, which not only enable visualization of diseased cells but also induce therapeutic cellular responses, are essential to biological studies. In the current work, a conjugated polyelectrolyte, PPET3-N2, was designed and synthesized as a dual-functional probe. The poly(phenylene ethynylene) terthiophene polymer backbone contributes to the polymer's light-harvesting property to ensure the strong fluorescence as well as photosensitization, whereas quantanary ammonium side chains interact with target organelle for localization...
March 29, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28276242/cellular-uptake-mechanism-of-cationic-branched-polypeptides-with-poly-l-lys-backbone
#13
Rita Szabó, Mónika Sebestyén, György Kóczán, Ádám Orosz, Gábor Mező, Ferenc Hudecz
Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK))...
March 9, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28275187/tight-junction-protein-occludin-is-a-porcine-epidemic-diarrhea-virus-entry-factor
#14
Xiaolei Luo, Longjun Guo, Jian Zhang, Yunfei Xu, Weihong Gu, Li Feng, Yue Wang
Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although it was long believed to replicate in the intestinal epithelium using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells resulted in the disruption of the tight junctional distribution of occludin to the intracellular localization. Overexpression of occludin in target cells makes them more susceptible for PEDV infection, whereas ablation of occludin expression using siRNA in target cells significantly reduces their susceptibility to virus infection...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250131/measles-virus-enters-breast-and-colon-cancer-cell-lines-through-a-pvrl4-mediated-macropinocytosis-pathway
#15
Sebastien Delpeut, Gary Sisson, Karen M Black, Christopher D Richardson
Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease, but has emerged as a promising oncolytic platform. Previous studies of MeV entry have focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express MeV receptors, SLAM (Signaling Lymphocyte-Activating Molecule) and PVRL4 (Poliovirus Receptor-Like-4, nectin-4)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250113/cxcl12-induced-macropinocytosis-modulates-two-distinct-pathways-to-activate-mtorc1-in-macrophages
#16
Regina Pacitto, Isabella Gaeta, Joel A Swanson, Sei Yoshida
Although growth factors and chemokines elicit different overall effects on cells-growth and chemotaxis, respectively-and activate distinct classes of cell-surface receptors, nonetheless, they trigger similar cellular activities and signaling pathways. The growth factor M-CSF and the chemokine CXCL12 both stimulate the endocytic process of macropinocytosis, and both activate the mechanistic target of rapamycin complex 1 (mTORC1), a protein complex that regulates cell metabolism. Recent studies of signaling by M-CSF in macrophages identified a role for macropinocytosis in the activation of mTORC1, in which delivery of extracellular amino acids into lysosomes via macropinocytosis was required for activation of mTORC1...
March 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#17
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#18
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
May 2017: Biomaterials
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#19
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28223800/comparison-of-the-cellular-transport-mechanism-of-cationic-star-shaped-polymers-and-liposomes-in-hacat-cells
#20
COMPARATIVE STUDY
Heng-Cong Luo, Na Li, Li Yan, Kai-Jin Mai, Kan Sun, Wei Wang, Guo-Juan Lao, Chuan Yang, Li-Ming Zhang, Meng Ren
Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine(®) 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction...
2017: International Journal of Nanomedicine
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