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Endosomal trafficking

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https://www.readbyqxmd.com/read/29331806/unifying-in%C3%A2-vitro-and-in%C3%A2-vivo-ivt-mrna-expression-discrepancies-in-skeletal-muscle-via-mechanotransduction
#1
Sushma M Bhosle, Kristin H Loomis, Jonathan L Kirschman, Emmeline L Blanchard, Daryll A Vanover, Chiara Zurla, Damien Habrant, Darin Edwards, Patrick Baumhof, Bruno Pitard, Philip J Santangelo
The translational efficiency of an in vitro transcribed (IVT) mRNA was measured upon delivery to primary skeletal muscle cells and to a mouse model system, towards the development of a predictive in vitro assay for the screening and validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered either naked or complexed with novel aminoglycoside-based delivery vehicles, significant differences in protein expression in vitro and in vivo were observed. We hypothesized that this previously anticipated discrepancy was due to differences in the mechanism of IVT mRNA endosomal entry and release following delivery...
January 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331581/identification-and-characterization-of-arginine-finger-like-motifs-and-endosome-lysosome-basolateral-sorting-signals-within-ectopically-expressed-cira-a-coxiella-burnetii-type-iv-secreted-effector-protein
#2
Mary M Weber, Robert Faris, Erin J van Schaik, James E Samuel
Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro...
January 10, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29331069/cellular-membrane-trafficking-machineries-utilized-by-the-hepatitis-viruses
#3
REVIEW
Jun Inoue, Masashi Ninomiya, Tooru Shimosegawa, Mark A McNiven
While the life cycles of hepatitis viruses (hepatitis A, B, C, D, and E viruses) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses 'hijack' the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known as a leading cause of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating HCV patients have recently been made, patients with HBV continue to require life-long treatment, which makes a thorough understanding of the HBV life cycle essential...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29324305/caveolin-mediated-endocytosis-of-the-chlamydia-m278-outer-membrane-peptide-encapsulated-in-poly-lactic-acid-poly-ethylene-glycol-nanoparticles-by-mouse-primary-dendritic-cells-enhances-specific-immune-effectors-mediated-by-mhc-class-ii-and-cd4-t-cells
#4
Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules...
December 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29322087/the-endosomal-protein-endotubin-is-required-for-enterocyte%C3%A2-differentiation
#5
Christopher M Cox, Ruifeng Lu, Kaan Salcin, Jean M Wilson
Background & Aims: During late embryonic development and through weaning, enterocytes of the ileum are highly endocytic. Defects in endocytosis and trafficking are implicated in neonatal disease, however, the mechanisms regulating trafficking during the developmental period are incompletely understood. The apical endosomal protein endotubin (EDTB) is highly expressed in the late embryonic and neonatal ileum. In epithelial cells in vitro, EDTB regulates both trafficking of tight junction proteins and proliferation through modulation of YAP activity...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29321327/human-papillomavirus-16-infection-induces-vap-dependent-endosomal-tubulation
#6
Abida Siddiqa, Paola Massimi, David Pim, Justyna Broniarczyk, Lawrence Banks
Human Papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317286/the-a-enth-domain-containing-protein-ateca4-is-an-adaptor-protein-involved-in-cargo-recycling-from-the-trans-golgi-network-early-endosome-to-the-plasma-membrane
#7
Hong Hanh Nguyen, Myoung Hui Lee, Kyungyoung Song, Gyeongik Ahn, Jihyeong Lee, Inhwan Hwang
Endocytosis and subsequent trafficking pathways are crucial for regulating the activity of plasma membrane-localized proteins. Depending on cellular and physiological conditions, the internalized cargoes are sorted at (and transported from) the trans-Golgi network/early endosome (TGN/EE) to the vacuole for degradation or recycled back to the plasma membrane. How this occurs at the molecular level remains largely elusive. Here we provide evidence that the ENTH domain-containing protein AtECA4 plays a crucial role in recycling cargoes from the TGN/EE to the plasma membrane...
January 6, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29313392/improved-intestinal-absorption-of-paclitaxel-by-mixed-micelles-self-assembled-from-vitamin-e-succinate-based-amphiphilic-polymers-and-their-transcellular-transport-mechanism-and-intracellular-trafficking-routes
#8
Xiaoyou Qu, Yang Zou, Chuyu He, Yuanhang Zhou, Yao Jin, Yunqiang Deng, Ziqi Wang, Xinru Li, Yanxia Zhou, Yan Liu
To ensure that antitumor drugs can be effectively transported across intestinal barrier and then quickly released in tumor cells, mixed polymeric micelles (Mix-PMs) were designed and fabricated by combining poly(2-ethyl-2-oxazoline)-vitamin E succinate (PEOz-VES) with TPGS1000 for enhancing intestinal absorption of paclitaxel. PEOz-VES exhibited an extremely low critical micelle concentration and negligible cytotoxicity. The Mix-PMs were characterized to have about 20 nm in diameter, uniform spherical morphology, high drug-loading content and sustained drug release profile with a retained pH-sensitivity...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29312605/overexpression-of-scamp3-is-an-indicator-of-poor-prognosis-in-hepatocellular-carcinoma
#9
Xinyuan Zhang, Jie Sheng, Yuhong Zhang, Yu Tian, Jie Zhu, Nan Luo, Congshu Xiao, Rongkuan Li
SCAMP3, an isoform of the secretory carrier membrane proteins (SCAMPs) family, is a membrane-trafficking protein involved in endosome transport. Previous microarray data showed that SCAMP3 mRNA is highly expressed in hepatocellular carcinoma (HCC). In this study, the expression and clinical significance of SCAMP3 in 100 pairs of HCC and adjacent normal tissue were investigated. siRNA transfection was performed to silence SCAMP3 expression in HCC cells. The MTS assay and flow cytometry were used to detect the proliferation, cell cycle progression of HCC cells...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311744/mutations-in-vps15-perturb-neuronal-migration-in-mice-and-are-associated-with-neurodevelopmental-disease-in-humans
#10
Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H Hansen, Ratna Tripathy, Anna K Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M Keane, Johannes Zuber, David J Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A Keays
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling...
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29311259/the-endosomal-trafficking-factors-corvet-and-escrt-suppress-plasma-membrane-residence-of-the-renal-outer-medullary-potassium-channel-romk
#11
Timothy D Mackie, Bo-Young Kim, Arohan R Subramanya, Daniel J Bain, Allyson F O'Donnell, Paul A Welling, Jeffrey L Brodsky
Protein trafficking can act as the primary regulatory mechanism for ion channels with high open probabilities, such as the renal outer medullary (ROMK) channel. ROMK, also known as Kir1.1 (KCNJ1), is the major route for potassium secretion into the pro-urine and plays an indispensable role in regulating serum potassium and urinary concentrations. However, the cellular machinery that regulates ROMK trafficking has not been fully defined. To identify regulators of the cell-surface population of ROMK, we expressed a pH-insensitive version of the channel in the budding yeast Saccharomyces cerevisiae...
January 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29306078/effect-of-fish-oil-on-agonist-induced-receptor-internalization-of-the-pg-f2%C3%AE-receptor-and-cell-signaling-in-bovine-luteal-cells-in%C3%A2-vitro
#12
M R Plewes, P D Burns
Many receptors span the plasma membrane allowing for signal transduction, converting extracellular signals into intracellular signals. Following ligand-induced activation, membrane-bound receptors are taken into endocytic vesicles, where they are targeted for degradation or recycled back to the plasma membrane. The objectives of the present study were to determine the influence of fish oil on (1) PGF2α-induced receptor internalization and trafficking of the PGF2α (FP) receptor, (2) cytoskeletal structural integrity, and (3) PGF2α-induced mitogen-activated protein kinase (MAPK) signaling in bovine luteal cells...
December 12, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29303993/endolysosomal-cation-channels-and-cancer-a-link-with-great-potential
#13
REVIEW
Christian Grimm, Karin Bartel, Angelika M Vollmar, Martin Biel
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism...
January 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29303184/the-combination-of-endolysosomal-escape-and-basolateral-stimulation-to-overcome-the-difficulties-of-easy-uptake-hard-transcytosis-of-ligand-modified-nanoparticles-in-oral-drug-delivery
#14
Yi Cui, Wei Shan, Rui Zhou, Min Liu, Lei Wu, Quan Guo, Yaxian Zheng, Jiawei Wu, Yuan Huang
Ligand-modified nanoparticles (NPs) are an effective tool to increase the endocytosis efficiency of drugs, but these functionalized NPs face the drawback of "easy uptake hard transcytosis" in the oral delivery of proteins and peptides. Adversely, the resulting deficiency in transcytosis has not attracted much attention. Herein, NPs modified with the low-density lipoprotein receptor (LDLR) ligand NH2-C6-[cMPRLRGC]c-NH2, i.e., peptide-22 (P22NPs) were fabricated to investigate strategies related to the enhancement of transcytosis...
January 5, 2018: Nanoscale
https://www.readbyqxmd.com/read/29301854/autophagy-is-required-for-sortilin-mediated-degradation-of-apolipoprotein-b100
#15
Jaume Amengual, Liang Guo, Alanna Strong, Julio Madrigal-Matute, Haizhen Wang, Susmita Kaushik, Jeffrey L Brodsky, Daniel J Rader, Ana Maria Cuervo, Edward A Fisher
Rationale: Genome-Wide Association Studies identified single nucleotide polymorphisms (SNPs) near the SORT1 locus strongly associated with decreased plasma low-density lipoprotein cholesterol (LDL-C) levels and protection from atherosclerotic cardiovascular disease and myocardial infarction. The minor allele of the causal SORT1 SNP locus creates a putative C/EBPα binding site in the SORT1 promoter, thereby increasing sortilin expression by 12-fold in liver, which is rich in this transcription factor. Our previous studies in mice have showed reductions in plasma LDL-C and its principal protein component, apolipoprotein B (apoB) with increased SORT1 expression, and in vitro studies suggested that sortilin promoted the presecretory lysosomal degradation of apoB associated with the LDL precursor, very-low density lipoprotein (VLDL)...
January 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29296759/a-specialized-pathway-for-erythroid-iron-delivery-through-lysosomal-trafficking-of-transferrin-receptor-2
#16
Shadi Khalil, Maja Holy, Stephen Grado, Robert Fleming, Ryo Kurita, Yukio Nakamura, Adam Goldfarb
Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released, reduced, and exported to the cytosol via DMT1. However, mice lacking TfR1 or DMT1 demonstrate residual erythropoiesis, suggesting additional pathways for iron use...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288738/vacuole-integrity-maintained-by-duf300-proteins-is-required-for-brassinosteroid-signaling-regulation
#17
Qinsong Liu, Thomas Vain, Corrado Viotti, Siamsa M Doyle, Danuše Tarkowská, Ondřej Novák, Cyril Zipfel, Folke Sitbon, Stéphanie Robert, Daniel Hofius
Brassinosteroid (BR) hormone signaling controls multiple processes during plant growth and development and is initiated at the plasma membrane through the receptor kinase BRASSINOSTEROID INSENSITIVE1 (BRI1) together with co-receptors such as BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1). BRI1 abundance is regulated by endosomal recycling and vacuolar targeting, but the role of vacuole-related proteins in BR receptor dynamics and BR responses remain elusive. Here, we show that the absence of two DUF300 domain-containing tonoplast proteins, LAZARUS1 (LAZ1) and LAZ1 HOMOLOG1 (LAZ1H1), causes vacuole morphology defects, growth inhibition, and constitutive activation of BR signaling...
December 27, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29285208/rab-coupling-protein-mediated-endosomal-recycling-of-n-cadherin-influences-cell-motility
#18
Andrew J Lindsay, Mary W McCaffrey
Rab coupling protein (RCP) is a Rab GTPase effector that functions in endosomal recycling. The RCP gene is frequently amplified in breast cancer, leading to increased cancer aggressiveness. Furthermore, RCP enhances the motility of ovarian cancer cells by coordinating the recycling of α5β1 integrin and EGF receptor to the leading edge of migrating cells. Here we report that RCP also influences the motility of lung adenocarcinoma cells. Knockdown of RCP inhibits the motility of A549 cells in 2D and 3D migration assays, while its overexpression enhances migration in these assays...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#19
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
https://www.readbyqxmd.com/read/29282322/antagonistic-regulation-of-trafficking-to-caenorhabditis-elegans-sensory-cilia-by-a-retinal-degeneration-3-homolog-and-retromer
#20
Luis A Martínez-Velázquez, Niels Ringstad
Sensory neurons often possess cilia with elaborate membrane structures that are adapted to the sensory modality of the host cell. Mechanisms that target sensory transduction proteins to these specialized membrane domains remain poorly understood. Here, we show that a homolog of the human retinal dystrophy gene Retinal Degeneration 3 (RD3) is a Golgi-associated protein required for efficient trafficking of a sensory receptor, the receptor-type guanylate cyclase GCY-9, to cilia in chemosensory neurons of the nematode Caenorhabditis elegans The trafficking defect caused by mutation of the nematode RD3 homolog is suppressed in vivo by mutation of key components of the retromer complex, which mediates recycling of cargo from endosomes to the Golgi...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
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