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Macropinocytosis

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https://www.readbyqxmd.com/read/27909711/effect-of-partial-pegylation-on-particle-uptake-by-macrophages
#1
Lucero Sanchez, Yi Yi, Yan Yu
Controlling the internalization of synthetic particles by immune cells remains a grand challenge for developing successful drug carrier systems. Polyethylene glycol (PEG) is frequently used as a protective coating on particles to evade immune clearance, but it also hinders the interactions of particles with their intended target cells. In this study, we investigate a spatial decoupling strategy, in which PEGs are coated on only one hemisphere of particles, so that the other hemisphere is available for functionalization of cell-targeting ligands without the hindrance effect from the PEGs...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27892481/autophagy-is-required-for-pdac-glutamine-metabolism
#2
Ju-Won Seo, Jungwon Choi, So-Yeon Lee, Suhyun Sung, Hyun Ju Yoo, Min-Ji Kang, Heesun Cheong, Jaekyoung Son
Macroautophagy (autophagy) is believed to maintain energy homeostasis by degrading unnecessary cellular components and molecules. Its implication in regulating cancer metabolism recently started to be uncovered. However, the precise roles of autophagy in cancer metabolism are still unclear. Here, we show that autophagy plays a critical role in glutamine metabolism, which is required for tumor survival. Pancreatic ductal adenocarcinoma (PDAC) cells require both autophagy and typical glutamine transporters to maintain intracellular glutamine levels...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883055/gapmer-cellular-internalization-by-macropinocytosis-induces-sequence-specific-gene-silencing-in-human-primary-t-cells
#3
Mobashar Hussain Urf Turabe Fazil, Seow Theng Ong, Madhavi Latha Somaraju Chalasani, Jian Hui Low, Atish Kizhakeyil, Akshay Mamidi, Carey Fang Hui Lim, Graham D Wright, Rajamani Lakshminarayanan, Dermot Kelleher, Navin Kumar Verma
Post-transcriptional gene silencing holds great promise in discovery research for addressing intricate biological questions and as therapeutics. While various gene silencing approaches, such as siRNA and CRISPR-Cas9 techniques, are available, these cannot be effectively applied to "hard-to-transfect" primary T-lymphocytes. The locked nucleic acid-conjugated chimeric antisense oligonucleotide, called "GapmeR", is an emerging new class of gene silencing molecule. Here, we show that GapmeR internalizes into human primary T-cells through macropinocytosis...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872138/micrornas-103-107-coordinately-regulate-macropinocytosis-and-autophagy
#4
Jong Kook Park, Han Peng, Julia Katsnelson, Wending Yang, Nihal Kaplan, Ying Dong, Joshua Z Rappoport, CongCong He, Robert M Lavker
Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy, the lysosome-based catabolic process, involve vesicular biogenesis (early stage) and turnover (end stage). Much is known about early-stage events; however, our understanding of how the end stages of these processes are governed is incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family, which is preferentially expressed in the stem cell-enriched limbal epithelium, coordinately regulates aspects of both these activities...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#5
Lei Tan, Yuqiang Zhang, Yuan Zhan, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao, Chan Ding
Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#6
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27835596/cd99-triggering-induces-methuosis-of-ewing-sarcoma-cells-through-igf-1r-ras-rac1-signaling
#7
Maria Cristina Manara, Mario Terracciano, Caterina Mancarella, Marika Sciandra, Clara Guerzoni, Michela Pasello, Andrea Grilli, Nicoletta Zini, Piero Picci, Mario P Colombo, Andrea Morrione, Katia Scotlandi
CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829452/genetic-impairment-of-parasite-myosin-motors-uncovers-the-contribution-of-host-cell-membrane-dynamics-to-toxoplasma-invasion-forces
#8
Marion Bichet, Bastien Touquet, Virginie Gonzalez, Isabelle Florent, Markus Meissner, Isabelle Tardieux
BACKGROUND: The several-micrometer-sized Toxoplasma gondii protozoan parasite invades virtually any type of nucleated cell from a warm-blooded animal within seconds. Toxoplasma initiates the formation of a tight ring-like junction bridging its apical pole with the host cell membrane. The parasite then actively moves through the junction into a host cell plasma membrane invagination that delineates a nascent vacuole. Recent high resolution imaging and kinematics analysis showed that the host cell cortical actin dynamics occurs at the site of entry while gene silencing approaches allowed motor-deficient parasites to be generated, and suggested that the host cell could contribute energetically to invasion...
November 9, 2016: BMC Biology
https://www.readbyqxmd.com/read/27827955/a-novel-role-of-dickkopf-related-protein-3-in-macropinocytosis-in-human-bladder-cancer-t24-cells
#9
Nonoka Tsujimura, Nami O Yamada, Yuki Kuranaga, Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi, Yukihiro Akao
Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G₀/G₁ cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA)...
November 5, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821733/a-diaphanous-related-formin-links-ras-signaling-directly-to-actin-assembly-in-macropinocytosis-and-phagocytosis
#10
Alexander Junemann, Vedrana Filić, Moritz Winterhoff, Benjamin Nordholz, Christof Litschko, Helena Schwellenbach, Till Stephan, Igor Weber, Jan Faix
Phagocytosis and macropinocytosis are Ras-regulated and actin-driven processes that depend on the dynamic rearrangements of the plasma membrane that protrudes and internalizes extracellular material by cup-shaped structures. However, the regulatory mechanisms underlying actin assembly in large-scale endocytosis remain elusive. Here, we show that the Diaphanous-related formin G (ForG) from the professional phagocyte Dictyostelium discoideum localizes to endocytic cups. Biochemical analyses revealed that ForG is a rather weak nucleator but efficiently elongates actin filaments in the presence of profilin...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27818713/mechanism-of-enhanced-cellular-uptake-and-cytosolic-retention-of-mk2-inhibitory-peptide-nano-polyplexes
#11
Kameron V Kilchrist, Brian C Evans, Colleen M Brophy, Craig L Duvall
Electrostatic complexation of a cationic MAPKAP kinase 2 inhibitory (MK2i) peptide with the anionic, pH-responsive polymer poly(propylacrylic acid) (PPAA) yields MK2i nano-polyplexes (MK2i-NPs) that significantly increase peptide uptake and intracellular retention. This study focused on elucidating the mechanism of MK2i-NP cellular uptake and intracellular trafficking in vascular smooth muscle cells. Small molecule inhibition of various endocytic pathways showed that MK2i-NP cellular uptake involves both macropinocytosis and clathrin mediated endocytosis, whereas the free peptide exclusively utilizes clathrin mediated endocytosis for cell entry...
September 2016: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/27818203/cytotoxicity-of-prion-protein-derived-cell-penetrating-peptides-is-modulated-by-ph-but-independent-of-amyloid-formation
#12
Vineeth Mukundan, Christy Maksoudian, Maria C Vogel, Ibrahim Chehade, Marios S Katsiotis, Saeed M Alhassan, Mazin Magzoub
Prion diseases are associated with conversion of cellular prion protein (PrP(C)) into an abnormally folded and infectious scrapie isoform (PrP(Sc)). We previously showed that peptides derived from the unprocessed N-termini of mouse and bovine prion proteins, mPrP1-28 and bPrP1-30, function as cell-penetrating peptides (CPPs), and destabilize model membrane systems, which could explain the infectivity and toxicity of prion diseases. However, subsequent studies revealed that treatment with mPrP1-28 or bPrP1-30 significantly reduce PrP(Sc) levels in prion-infected cells...
November 3, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27810441/lipid-modified-oligonucleotide-conjugates-insights-into-gene-silencing-interaction-with-model-membranes-and-cellular-uptake-mechanisms
#13
Begoña Ugarte-Uribe, Santiago Grijalvo, Samuel Núñez Pertíñez, Jon V Busto, César Martín, Adele Alagia, Félix M Goñi, Ramón Eritja, Itziar Alkorta
The ability of oligonucleotides to silence specific genes or inhibit the biological activity of specific proteins has generated great interest in their use as research tools and therapeutic agents. Unfortunately, their biological applications meet the limitation of their poor cellular accessibility. Developing an appropriate delivery system for oligonucleotides is essential to achieve their efficient cellular uptake. In the present work a series of phosphorothioate lipid-oligonucleotide hybrids were synthesized introducing covalently single or double lipid tails at both 3'- and 5'-termini of an antisense oligonucleotide...
October 20, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27793999/glucocorticoid-induced-leucine-zipper-protein-controls-macropinocytosis-in-dendritic-cells
#14
Joseph Calmette, Matthieu Bertrand, Mathias Vétillard, Mehdi Ellouze, Shaun Flint, Valérie Nicolas, Armelle Biola-Vidamment, Marc Pallardy, Eric Morand, Françoise Bachelerie, Véronique Godot, Géraldine Schlecht-Louf
Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs...
October 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27791032/v-1-regulates-capping-protein-activity-in-vivo
#15
Goeh Jung, Christopher J Alexander, Xufeng S Wu, Grzegorz Piszczek, Bi-Chang Chen, Eric Betzig, John A Hammer
Capping Protein (CP) plays a central role in the creation of the Arp2/3-generated branched actin networks comprising lamellipodia and pseudopodia by virtue of its ability to cap the actin filament barbed end, which promotes Arp2/3-dependent filament nucleation and optimal branching. The highly conserved protein V-1/Myotrophin binds CP tightly in vitro to render it incapable of binding the barbed end. Here we addressed the physiological significance of this CP antagonist in Dictyostelium, which expresses a V-1 homolog that we show is very similar biochemically to mouse V-1...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27785019/ge11-peptide-modified-and-reduction-responsive-hyaluronic-acid-based-nanoparticles-induced-higher-efficacy-of-doxorubicin-for-breast-carcinoma-therapy
#16
Danrong Hu, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke, Tianyuan Ci
Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11-HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11-HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle's structure and accelerating the drug release dramatically in the presence of intracellular reductive environment...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27775687/macropinocytosis-of-type-xvii-collagen-induced-by-bullous-pemphigoid-igg-is-regulated-via-protein-kinase-c
#17
Hiroaki Iwata, Mayumi Kamaguchi, Hideyuki Ujiie, Machiko Nishimura, Kentaro Izumi, Ken Natsuga, Satoru Shinkuma, Wataru Nishie, Hiroshi Shimizu
Macropinocytosis is an endocytic pathway that is involved in the nonselective fluid uptake of extracellular fluid. Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies to type XVII collagen (COL17), which is a component of hemidesmosome. When keratinocytes are treated with BP-IgG, COL17 internalizes into cells by way of the macropinocytosis. We investigated the mechanism of COL17 macropinocytosis using DJM-1 cells, a cutaneous squamous cell carcinoma cell line...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27764233/escrt-i-protein-tsg101-plays-a-role-in-the-post-macropinocytic-trafficking-and-infection-of-endothelial-cells-by-kaposi-s-sarcoma-associated-herpesvirus
#18
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27748399/vectorization-of-biomacromolecules-into-cells-using-extracellular-vesicles-with-enhanced-internalization-induced-by-macropinocytosis
#19
Ikuhiko Nakase, Kosuke Noguchi, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs, exosomes) are approximately 30- to 200-nm-long vesicles that have received increased attention due to their role in cell-to-cell communication. Although EVs are highly anticipated to be a next-generation intracellular delivery tool because of their pharmaceutical advantages, including non-immunogenicity, their cellular uptake efficacy is low because of the repulsion of EVs and negatively charged cell membranes and size limitations in endocytosis. Here, we demonstrate a methodology for achieving enhanced cellular EV uptake using arginine-rich cell-penetrating peptides (CPPs) to induce active macropinocytosis...
October 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27744707/optimization-of-curcumin-loaded-peg-plga-nanoparticles-by-gsh-functionalization-investigation-of-the-internalization-pathway-in-neuronal-cells
#20
Ghislain Djiokeng Paka, Charles Ramassamy
One major challenge in the field of nanotherapeutics is to increase the selective delivery of cargo to targeted cells. Using Poly Lactic-co-Glycolic Acid (PLGA), we recently highlighted the importance of polymer composition in the biological fate of the nanodrug delivery systems. However the route of internalisation of polymeric nanoparticles (NPs) is another key component to consider in the elaboration of modern and targeted devices. For that purpose, herein, we effectively synthesized and characterised glutathione- functionalized PLGA-nanoparticles (GSH-NPs) loaded with curcumin (GSH-NPs-Cur), using thiol-maleimide click reaction and determined their physicochemical properties...
October 15, 2016: Molecular Pharmaceutics
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