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Endocytic trafficking

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https://www.readbyqxmd.com/read/27925633/shock-wave-enhances-angiogenesis-through-vegfr2-activation-and-recycling
#1
Tien-Hung Huang, Cheuk-Kwan Sun, Yi-Ling Chen, Ching-Jen Wang, Tsung-Cheng Yin, Mel S Lee, Hon-Kan Yip
Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay...
December 6, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27909248/regulation-of-chemokine-receptor-ccr2-recycling-by-filamin-a-phosphorylation
#2
Mònica Pons, Ismael Izquierdo, Mireia Andreu-Carbó, Georgina Garrido, Jesús Planagumà, Olivia Muriel, M Isabel Geli, Anna M Aragay
Proper endosomal trafficking of ligand-activated G protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B), endocytic recycling is important to sustain monocyte migration; while filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27900285/a-t4ss-effector-targets-host-cell-alpha-enolase-contributing-to-brucella-abortus-intracellular-lifestyle
#3
María I Marchesini, Susana M Morrone Seijo, Francisco F Guaimas, Diego J Comerci
Brucella abortus, the causative agent of bovine brucellosis, invades and replicates within cells inside a membrane-bound compartment known as the Brucella containing vacuole (BCV). After trafficking along the endocytic and secretory pathways, BCVs mature into endoplasmic reticulum-derived compartments permissive for bacterial replication. Brucella Type IV Secretion System (VirB) is a major virulence factor essential for the biogenesis of the replicative organelle. Upon infection, Brucella uses the VirB system to translocate effector proteins from the BCV into the host cell cytoplasm...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27899655/visualization-of-self-delivering-hydrophobically-modified-sirna-cellular-internalization
#4
Socheata Ly, Deanna M Navaroli, Marie-Cécile Didiot, James Cardia, Lakshmipathi Pandarinathan, Julia F Alterman, Kevin Fogarty, Clive Standley, Lawrence M Lifshitz, Karl D Bellve, Matthieu Prot, Dimas Echeverria, Silvia Corvera, Anastasia Khvorova
siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs(®)) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899122/endocytosed-nanoparticles-hold-endosomes-and-stimulate-binucleated-cells-formation
#5
Lin Xia, Weihong Gu, Mingyi Zhang, Ya-Nan Chang, Kui Chen, Xue Bai, Lai Yu, Juan Li, Shan Li, Gengmei Xing
BACKGROUND: Nanotechnology developed rapidly in cellular diagnosis and treatment, the endocytic system was an important pathway for targeting cell. In the research of developing macrophages as drug carriers or important therapeutic targets, an interesting phenomenon, internalized nanoparticles induced to form binucleated macrophages, was found although the particles dose did not cause obvious cytotoxicity. RESULTS: Under 25 μg/ml, internalized 30 nm polystyrene beads(30 nm Ps nanoparticles) induced the formation of binucleated macrophages when they entered into endosomes via the endocytic pathway...
November 29, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27895104/bin1-and-cd2ap-polarise-the-endocytic-generation-of-beta-amyloid
#6
Florent Ubelmann, Tatiana Burrinha, Laura Salavessa, Ricardo Gomes, Cláudio Ferreira, Nuno Moreno, Cláudia Guimas Almeida
The mechanisms driving pathological beta-amyloid (Aβ) generation in late-onset Alzheimer's disease (AD) are unclear. Two late-onset AD risk factors, Bin1 and CD2AP, are regulators of endocytic trafficking, but it is unclear how their endocytic function regulates Aβ generation in neurons. We identify a novel neuron-specific polarisation of Aβ generation controlled by Bin1 and CD2AP We discover that Bin1 and CD2AP control Aβ generation in axonal and dendritic early endosomes, respectively. Both Bin1 loss of function and CD2AP loss of function raise Aβ generation by increasing APP and BACE1 convergence in early endosomes, however via distinct sorting events...
November 28, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27888097/rab7a-regulates-cell-migration-through-rac1-and-vimentin
#7
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27879341/title-dynamin-functions-and-ligands-classical-mechanism-behind
#8
Mahaveer Singh, Hemant Jadhav, Tanya B
Dynamin is a GTPase, which plays a vital role in clathrin dependent endocytosis and other vesicular trafficking processes. Dynamin acts as scissor with debatable mechanism for newly formed vesicles originating from plasma membrane. Dynamin related proteins are important components in scission of various organelles such as clathrin coated vesicles, phagosomes and mitochondria, etc. helping in organelle division, viral resistance and mitochondrial fusion/division. Dysfunction and mutations in dynamin have been implicated in various disorders, where endocytic trafficking is involved, such as Alzheimer's, Parkinson's, Huntington's, Charcot-Marie Tooth disease, Heart failure, Schizophrenia, Epilepsy, Cancer, Optic atrophy, Down syndrome, Osteoporosis etc...
November 22, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27872253/gtpase-cross-talk-regulates-trappii-activation-of-rab11-homologues-during-vesicle-biogenesis
#9
Laura L Thomas, J Christopher Fromme
Rab guanosine triphosphatases (GTPases) control cellular trafficking pathways by regulating vesicle formation, transport, and tethering. Rab11 and its paralogs regulate multiple secretory and endocytic recycling pathways, yet the guanine nucleotide exchange factor (GEF) that activates Rab11 in most eukaryotic cells is unresolved. The large multisubunit transport protein particle (TRAPP) II complex has been proposed to act as a GEF for Rab11 based on genetic evidence, but conflicting biochemical experiments have created uncertainty regarding Rab11 activation...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27872251/regulation-of-egfr-surface-levels-by-copii-dependent-trafficking
#10
Hesso Farhan
Cell surface levels of epidermal growth factor receptors (EGFRs) are thought to be controlled mainly by endocytic trafficking, with biosynthetic EGFR trafficking presumed to be a constitutive and unregulated process. However, Scharaw et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201601090) demonstrate a role for inducible COPII trafficking in controlling EGFR surface levels.
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27864431/apol1-mediated-cell-injury-involves-disruption-of-conserved-trafficking-processes
#11
Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27863541/cellular-endocytic-compartment-localization-of-expressed-canine-cd1-molecules
#12
Mette Schjaerff, Stefan M Keller, Verena K Affolter, Annemarie T Kristensen, Peter F Moore
CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and present a variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that survey distinct cellular compartments allowing for recognition of a large repertoire of lipids. The canine CD1 family consists of seven functional CD1 molecules (canine CD1a2, CD1a6, CD1a8, CD1a9, CD1b, CD1c and CD1e) and one presumed non-functional isoform (canine CD1d) due to a disrupted gene structure...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27863218/discovery-of-ibomycin-a-potent-antifungal-weapon
#13
J Andrew Alspaugh
In this issue of Cell Chemical Biology, Robbins et al. (2016) identify ibomycin, a unique compound with antifungal activity. Microbial physiological and genetic studies suggest that endocytic trafficking might be the site of action for this lead antifungal compound.
November 17, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#14
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/27861124/rab22a-controls-mhc-i-intracellular-trafficking-and-antigen-cross-presentation-by-dendritic-cells
#15
Ignacio Cebrian, Cristina Croce, Néstor A Guerrero, Nicolas Blanchard, Luis S Mayorga
Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8(+) T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e., Toxoplasma gondii) and tumors. To achieve efficient cross-presentation, dendritic cells (DCs) have specialized endocytic pathways; however, the molecular effectors involved are poorly understood. In this work, we identify the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27849881/239-lrp1-an-endocytic-vesicle-trafficking-protein-associated-with-chd-an-unexplored-pathway
#16
Jiuann-Huey Lin, Anupma Jha, Jacob McClreary, Cecilia Lo
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27822587/disruption-of-endolysosomal-trafficking-pathways-in-glioma-cells-by-methuosis-inducing-indole-based-chalcones
#17
Nneka E Mbah, Jean H Overmeyer, William A Maltese
Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes...
November 7, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27818713/mechanism-of-enhanced-cellular-uptake-and-cytosolic-retention-of-mk2-inhibitory-peptide-nano-polyplexes
#18
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/27818247/gapdh-binds-akt-to-facilitate-cargo-transport-in-the-early-secretory-pathway
#19
Ellen J Tisdale, Nikunj K Talati, Cristina R Artalejo, Assia Shisheva
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) undergoes numerous post-translational modifications, which impart new function and influence intracellular location. For example, atypical PKC ι/λ phosphorylates GAPDH that locates to vesicular tubular clusters and is required for retrograde membrane trafficking in the early secretory pathway. GAPDH is also required in the endocytic pathway; substitution of Pro(234) to Ser (Pro(234)Ser) rendered CHO cells defective in endocytosis. To determine if GAPDH (Pro(234)Ser) could inhibit endoplasmic reticulum to Golgi trafficking, we introduced the recombinant mutant enzyme into several biochemical and morphological transport assays...
December 10, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27811356/spatio-temporal-regulation-of-egfr-signaling-by-the-eps15-homology-domain-containing-protein-3-ehd3
#20
Mohamed Amessou, Abdul Shukkur Ebrahim, Ashok Dilly, Melvin Joseph, Marina Tabolina, Sahiti Chukkapalli, Louay Meroueh, Joseph T Syed, Allison Liddane, Siera Lanae Lang, Ayad Al-Katib, Mustapha Kandouz
The epidermal growth factor (EGF) receptor EGFR is a major receptor tyrosine kinase whose role in gliomagenesis is well established. We have recently identified EHD3 [Eps15 homology (EH) domain-containing protein 3], an endocytic trafficking regulatory protein, as a putative brain tumor suppressor. Here, we investigate the underlying mechanisms, by establishing a novel mechanistic and functional connection between EHD3 and the EGFR signaling pathway. We show that, in response to stimulation with the EGF ligand, EHD3 accelerates the rate of EGFR degradation by dramatically increasing its ubiquitination...
November 1, 2016: Oncotarget
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