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Cellular trafficking

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https://www.readbyqxmd.com/read/27913999/the-role-of-her2-egfr-and-other-receptor-tyrosine-kinases-in-breast-cancer
#1
Jennifer L Hsu, Mien-Chie Hung
Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913668/cellular-functions-of-lrrk2-implicate-vesicular-trafficking-pathways-in-parkinson-s-disease
#2
REVIEW
Mark R Cookson
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, associated with Parkinson's disease, have been shown to affect intracellular trafficking pathways in a variety of cells and organisms. An emerging theme is that LRRK2 can bind to multiple membranous structures in cells, and several recent studies have suggested that the Rab family of small GTPases might be important in controlling the recruitment of LRRK2 to specific cellular compartments. Once localized to membranes, LRRK2 then influences downstream events, evidenced by changes in the autophagy-lysosome pathway...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911100/mitochondria-and-iron-current-questions
#3
Bibbin T Paul, David H Manz, Frank M Torti, Suzy V Torti
Mitochondria are cellular organelles that perform numerous bioenergetic, biosynthetic, and regulatory functions and play a central role in iron metabolism. Extracellular iron is taken up by cells and transported to the mitochondria, where it is utilized for synthesis of cofactors essential to the function of enzymes involved in oxidation-reduction reactions, DNA synthesis and repair, and a variety of other cellular processes. Areas Covered: This article reviews the trafficking of iron to the mitochondria and normal mitochondrial iron metabolism, including heme synthesis and iron-sulfur cluster biogenesis...
December 2, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27905542/defining-an-olfactory-receptor-function-in-airway-smooth-muscle-cells
#4
William H Aisenberg, Jessie Huang, Wanqu Zhu, Premraj Rajkumar, Randy Cruz, Lakshmi Santhanam, Niranjana Natarajan, Hwan Mee Yong, Breann De Santiago, Jung Jin Oh, A-Rum Yoon, Reynold A Panettieri, Oliver Homann, John K Sullivan, Stephen B Liggett, Jennifer L Pluznick, Steven S An
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905431/the-snd-proteins-constitute-an-alternative-targeting-route-to-the-endoplasmic-reticulum
#5
Naama Aviram, Tslil Ast, Elizabeth A Costa, Eric C Arakel, Silvia G Chuartzman, Calvin H Jan, Sarah Haßdenteufel, Johanna Dudek, Martin Jung, Stefan Schorr, Richard Zimmermann, Blanche Schwappach, Jonathan S Weissman, Maya Schuldiner
In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27904144/causes-and-consequences-of-endoplasmic-reticulum-stress-in-rheumatic-disease
#6
REVIEW
Fatemeh Navid, Robert A Colbert
Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response...
December 1, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27903772/diverse-activities-of-viral-cis-acting-rna-regulatory-elements-revealed-using-multi-color-long-term-single-cell-imaging
#7
Ginger M Pocock, Laraine L Zimdars, Ming Yuan, Kevin W Eliceiri, Paul Ahlquist, Nathan M Sherer
Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other post-transcriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multi-color, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus) and an intron-retaining transcript encoded by the cellular NXF1 gene...
November 30, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27903224/evaluation-on-monocyte-mediated-delivery-of-a-therapeutic-gene-into-the-inflamed-brain
#8
Hsin-I Tong, Wen Kang, Guangzhou Zhou, Min Liu, Yingli Shi, Yuanan Lu
This study was aimed to explore the potential of a non-invasive monocytes-based delivery system to transport therapeutic genes into the diseased brain. The study was conducted by first establishing the optimized conditions for lentiviral vector (LV)-mediated gene transfer into freshly isolated monocytes, followed by investigating the inflamed-brain homing efficiency and in vivo cell-mediated transgene expression by carrier monocytes in a mouse model with acute subregional neuroinflammation. Using a newly optimized spin-infection method, up to 35% of freshly isolated monocytes were successfully transduced with the LV system DHIV-101 at M...
November 18, 2016: Current Gene Therapy
https://www.readbyqxmd.com/read/27902342/functional-analysis-of-a-viroid-rna-motif-mediating-cell-to-cell-movement-in-nicotiana-benthamiana
#9
Dongmei Jiang, Meng Wang, Shifang Li
Cell-to-cell trafficking through different cellular layers is a key process for various RNAs including those of plant viruses and viroids, but the regulatory mechanisms involved are still not fully elucidated and good model systems are important. Here, we analyze the function of a simple RNA motif (termed "loop19") in Potato spindle tuber viroid (PSTVd) which is required for trafficking in Nicotiana benthamiana leaves. Northern blotting, RT-PCR and in situ hybridization analyses demonstrated that unlike wild type PSTVd, which was present in the nuclei in all cell types, the trafficking-defective loop19 mutants were visible only in the nuclei of upper epidermal and palisade mesophyll cells, which shows that PSTVd loop19 plays a role in mediating RNA trafficking from palisade to spongy mesophyll cells in Nicotiana benthamiana leaves...
October 14, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901125/rab14-specifies-the-apical-membrane-through-arf6-mediated-regulation-of-lipid-domains-and-cdc42
#10
Ruifeng Lu, Jean M Wilson
The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899655/visualization-of-self-delivering-hydrophobically-modified-sirna-cellular-internalization
#11
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/27899652/production-of-dna-minicircles-less-than-250-base-pairs-through-a-novel-concentrated-dna-circularization-assay-enabling-minicircle-design-with-nf-%C3%AE%C2%BAb-inhibition-activity
#12
Thomas Thibault, Jeril Degrouard, Patrick Baril, Chantal Pichon, Patrick Midoux, Jean-Marc Malinge
Double-stranded DNA minicircles of less than 1000 bp in length have great interest in both fundamental research and therapeutic applications. Although minicircles have shown promising activity in gene therapy thanks to their good biostability and better intracellular trafficking, minicircles down to 250 bp in size have not yet been investigated from the test tube to the cell for lack of an efficient production method. Herein, we report a novel versatile plasmid-free method for the production of DNA minicircles comprising fewer than 250 bp...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899210/comparative-analysis-of-the-internalization-of-the-macrophage-receptor-sialoadhesin-in-human-and-mouse-primary-macrophages-and-cell-lines
#13
Marjorie De Schryver, Annelies Leemans, Isabel Pintelon, Davie Cappoen, Louis Maes, Guy Caljon, Paul Cos, Peter L Delputte
Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs...
November 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27899122/endocytosed-nanoparticles-hold-endosomes-and-stimulate-binucleated-cells-formation
#14
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/27897122/bioinformatics-analysis-of-chicken-mirnas-associated-with-monocyte-to-macrophage-differentiation-and-subsequent-ifng-stimulated-activation
#15
Kristopher Jl Irizarry, Adam Chan, Derek Kettle, Steven Kezian, Dominic Ma, Louis Palacios, Qingshun Li, Calvin L Keeler, Yvonne Drechsler
The goal of this project was to characterize the molecular and cellular roles of various gene targets regulated by 8 miRNAs in differentiating macrophages. Among a number of miRNAs that are found to be expressed in avian macrophages, we focused on eight specific miRNAs (miR-1618, miR-1586, miR-1633, miR-1627, miR-1646, miR-1649, miR-1610, miR-1647) associated with macrophage activation through Wnt signaling, ubiquitination, PPAR mediated macrophage function, vesicle mediated cytokine trafficking, and WD40 domain proteins in macrophage differentiation...
November 29, 2016: MicroRNA
https://www.readbyqxmd.com/read/27890631/evasion-of-host-immune-defenses-by-human-papillomavirus
#16
REVIEW
Joseph A Westrich, Cody J Warren, Dohun Pyeon
A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses...
November 24, 2016: Virus Research
https://www.readbyqxmd.com/read/27888307/monitoring-doxorubicin-cellular-uptake-and-trafficking-using-in-vitro-raman-microspectroscopy-short-and-long-time-exposure-effects-on-lung-cancer-cell-lines
#17
Zeineb Farhane, Franck Bonnier, Hugh J Byrne
Raman microspectroscopy is a non-invasive, in vitro analytical tool which is being increasingly explored for its potential in clinical applications and monitoring the uptake, mechanism of action and cellular interaction at a molecular level of chemotherapeutic drugs, ultimately as a potential label-free preclinical screening and companion diagnostic tool. In this study, doxorubicin (DOX), a "gold standard" chemotherapeutic drug, is employed as a model in the in vitro lung cancer cell line A549 in order to demonstrate the potential of Raman microspectroscopy to screen and identify spectroscopic markers of its trafficking and mechanism of action...
November 25, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27888097/rab7a-regulates-cell-migration-through-rac1-and-vimentin
#18
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 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27887991/vcp-p97-regulates-%C3%AE-2ar-quality-control-during-receptor-biosynthesis
#19
Richard Wargachuk, Irina Glazkova, Nicolas Audet, Darlaine Pétrin, Phan Trieu, Terence E Hébert
GPCRs form signalling complexes with other receptors as part of dimers, G proteins and effector partners. A proteomic screen to identify proteins that associate with the β2-adrenergic receptor (β2AR) identified many of components of the Endoplasmic-Reticulum-Associated Degradation (ERAD) quality control system [1], including the valosin-containing protein (VCP/p97). Here, we validated the interaction of VCP with co-expressed FLAG-β2AR, demonstrating, using an inducible expression system, that the interaction of FLAG-β2AR and VCP is not an artifact of overexpression of the β2AR per se...
November 22, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27881662/the-polycystins-are-modulated-by-cellular-oxygen-sensing-pathways-and-regulate-mitochondrial-function
#20
Valeria Padovano, Ivana Y Kuo, Lindsey K Stavola, Hans R Aerni, Benjamin J Flaherty, Hannah C Chapin, Ming Ma, Stefan Somlo, Alessandra Boletta, Barbara E Ehrlich, Jesse Rinehart, Michael J Caplan
Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum Ca(2+) release. Loss of PC1 expression profoundly alters cellular energy metabolism. The mechanisms that control the trafficking of PC1 and PC2 as well as their broader physiological roles remain poorly understood. We found that O2 levels regulate the subcellular localization and the channel activity of the polycystin complex through its interaction with the O2-sensing prolyl hydroxylase domain containing protein EGLN3 (or PHD3), which hydroxylates PC1...
November 23, 2016: Molecular Biology of the Cell
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