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Cell trafficking

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https://www.readbyqxmd.com/read/28819302/generation-and-intracellular-trafficking-of-a-polysialic-acid-carrying-fragment-of-the-neural-cell-adhesion-molecule-ncam-to-the-cell-nucleus
#1
Nina Westphal, Gabriele Loers, David Lutz, Thomas Theis, Ralf Kleene, Melitta Schachner
Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818525/whole-transcriptome-microarray-analysis-reveals-regulation-of-rab4-by-rbm5-in-neurons
#2
Travis C Jackson, Shawn E Kotermanski, Patrick M Kochanek
RNA binding motif 5 (RBM5) is a nuclear protein that modulates gene transcription and mRNA splicing in cancer cells. The brain is among the highest RBM5 expressing organ in the body but its mRNA target(s) or functions in the CNS have not been elucidated. Here we knocked down (KO) RBM5 in primary rat cortical neurons and analyzed total RNA extracts by gene microarray vs. neurons transduced with lentivirus to deliver control (non-targeting) shRNA. The mRNA levels of Sec23A (involved in ER-Golgi transport) and the small GTPase Rab4a (involved in endocytosis/protein trafficking) were increased in RBM5 KO neurons relative to controls...
August 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28818364/involvement-of-schrabgdi1-from-solanum-chilense-in-endocytic-trafficking-and-tolerance-to-salt-stress
#3
Alex San Martín-Davison, Ricardo Pérez-Díaz, Flavia Soto, José Madrid-Espinoza, Enrique González-Villanueva, Lorena Pizarro, Lorena Norambuena, Jaime Tapia, Hiromi Tajima, Eduardo Blumwald, Simón Ruiz-Lara
Physiological responses of plants to salinity stress requires the coordinated activation of many genes. A salt-induced gene was isolated from roots of the wild tomato species Solanum chilense and named SchRabGDI1 because it encodes a protein with high identity to GDP dissociation inhibitors of plants. These proteins are regulators of the RabGTPase cycle that play key roles in intracellular vesicular trafficking. The expression pattern of SchRabGDI1 showed an early up-regulation in roots and leaves under salt stress...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28817705/cell-surface-dynamics-and-cellular-distribution-of-endogenous-fcrn
#4
Lena D'Hooghe, Andrew D Chalmers, Sam Heywood, Paul Whitley
A major role for FcRn is the salvage of pinocytosed IgG and albumin from a degradative fate in lysosomes. FcRn achieves this by binding IgG in a pH-dependent manner in acidic endosomes and recycling it to the plasma membrane to be released at neutral pH. This is important in maintaining high serum IgG and albumin levels and has the potential to be exploited to modulate the pharmacokinetics of antibody-based therapeutics. Although FcRn is responsible for the recycling of IgG, the dynamic behaviour of endogenous FcRn is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28817270/magnetic-field-activated-sensing-of-mrna-in-living-cells
#5
Saira F Bakshi, Nataliia Guz, Andrey Zakharchenko, Han Deng, Alexei Tumanov, Craig D Woodworth, Sergiy Minko, Dmitry M Kolpashchikov, Evgeny Katz
Detection of specific mRNA in living cells has attracted significant attention in the last decade. Probes that can be easily delivered into cells and activated at the desired time can contribute to understand-ing translation, trafficking and degradation of mRNA. Here we report a new strategy termed Magnetic Field-Activated Binary De-oxyribozyme (MaBiDZ) sensor that enables both efficient delivery and temporal control of mRNA sensing by magnetic field. MaBiDZ uses two species of magnetic beads conjugated with different com-ponents of a multicomponent deoxyribozyme (DZ) sensor...
August 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28815533/hijacking-of-membrane-contact-sites-by-intracellular-bacterial-pathogens
#6
Isabelle Derré
Intracellular bacterial pathogens have evolved sophisticated mechanisms to hijack host cellular processes to promote their survival and replication inside host cells. Over the past two decades, much attention has been given to the strategies employed by these pathogens to manipulate various vesicular trafficking pathways. But in the past 5 years, studies have brought to light that intracellular bacteria also target non-vesicular trafficking pathways. Here we review how three vacuolar pathogens, namely, Legionella, Chlamydia, and Coxiella hijack components of cellular MCS with or without the formation of stable MCS...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815518/organelle-communication-at-membrane-contact-sites-mcs-from-curiosity-to-center-stage-in-cell-biology-and-biomedical-research
#7
Thomas Simmen, Mitsuo Tagaya
Cell biology has long recognized that organelles can communicate with each other. Initially, such communication was thought to occur primarily via vesicular trafficking between biochemically distinct organelles. However, studies starting in the 1970s on lipid metabolism have unearthed another way how organelles can communicate and have spawned the field of membrane contact sites (MCS). While, initially, MCS had been recognized as fluid entities that mediate lipid and ion transport in an ad hoc manner, more recently MCS have been found to depend on protein-protein interactions that control themselves a variety of MCS functions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815213/identification-of-rab18-as-an-essential-host-factor-for-bk-polyomavirus-infection-using-a-whole-genome-rna-interference-screen
#8
Linbo Zhao, Michael J Imperiale
BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins...
July 2017: MSphere
https://www.readbyqxmd.com/read/28815171/functional-analysis-of-na-h-exchanger-9-variants-identified-in-patients-with-autism-and-epilepsy
#9
Hari Prasad, James Osei-Owusu, Rajini Rao
Na(+)/H(+) exchanger isoform 9, NHE9, finely tunes the pH within the endosomal lumen to regulate cargo trafficking and turnover. In patients with autism, genetic approaches have revealed deletions, truncations and missense mutations in the gene encoding NHE9 (SLC9A9). To help establish causality, functional evaluation is needed to distinguish pathogenic mutations from harmless polymorphisms. Here, we evaluated three previously uncharacterized NHE9 variants, P117T, D496N, and Q609K reported in patients with autism and epilepsy...
April 2017: Matters (Zur)
https://www.readbyqxmd.com/read/28814834/intracellular-trafficking-of-new-anticancer-therapeutics-antibody-drug-conjugates
#10
REVIEW
Muhammad Kalim, Jie Chen, Shenghao Wang, Caiyao Lin, Saif Ullah, Keying Liang, Qian Ding, Shuqing Chen, Jinbiao Zhan
Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#11
Ryan T Sowell, Josef W Goldufsky, Magdalena Rogozinska, Zurisaday Quiles, Yanxia Cao, Eliseo F Castillo, Alison Finnegan, Amanda L Marzo
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814519/extracellular-matrix-proteins-mediate-hiv-1-gp120-interactions-with-%C3%AE-4%C3%AE-7
#12
David Plotnik, Wenjin Guo, Brad Cleveland, Priska von Haller, Jimmy K Eng, Miklos Guttman, Kelly K Lee, James Arthos, Shiu-Lok Hu
Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814501/knockout-of-the-golgi-stacking-proteins-grasp55-and-grasp65-impairs-golgi-structure-and-function
#13
Michael E Bekier, Leibin Wang, Jie Li, Haoran Huang, Danming Tang, Xiaoyan Zhang, Yanzhuang Wang
GRASP65 and GRASP55 were originally identified as Golgi stacking proteins; however, subsequent GRASP knockdown experiments yielded inconsistent results with respect to the Golgi structure, indicating a limitation of RNAi-based depletion. In this study, we have applied the recently developed CRISPR-Cas9 technology to knock out GRASP55 and GRASP65, individually or in combination, in HeLa and HEK293 cells. We show that double knockout of GRASP proteins disperses the Golgi stack into single cisternae and tubulovesicular structures, accelerates protein trafficking, and impairs accurate glycosylation of proteins and lipids...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#14
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812263/molecular-basis-of-oxytocin-receptor-signalling-in-the-brain-what-we-know-and-what-we-need-to-know
#15
Marta Busnelli, Bice Chini
Oxytocin (OT), a hypothalamic neuropeptide involved in regulating the social behaviour of all vertebrates, has been proposed as a treatment for a number of neuropsychiatric disorders characterised by deficits in the social domain. Over the last few decades, advances focused on understanding the social effects of OT and its role in physiological conditions and brain diseases, but much less has been done to clarify the molecular cascade of events involved in mediating such effects and in particular the cellular and molecular pharmacology of OT and its target receptor (OTR) in neuronal and glial cells...
August 16, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28811318/the-%C3%AE-cell-assassin-iapp-cytotoxicity
#16
Daniel Raleigh, Xiaoxue Zhang, Benoit Hastoy, Anne Clark
Islet amyloid polypeptide (IAPP) forms cytotoxic oligomers and amyloid fibrils in islets in Type 2 diabetes (T2DM). The causal factors for amyloid formation are largely unknown. Mechanisms of molecular folding and assembly of human IAPP (hIAPP) into β-sheets, oligomers and fibrils have been assessed by detailed biophysical studies of hIAPP and non-fibrillogenic, rodent IAPP (rIAPP); cytotoxicity is associated with the early phases (oligomers/multimers) of fibrillogenesis. Interaction with synthetic membranes promotes β-sheet assembly possibly via a transient α-helical molecular conformation...
August 15, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28811015/multiple-targeted-graphene-based-nanocarrier-for-intracellular-imaging-of-mrnas
#17
Ying Wang, Zhaohui Li, Misha Liu, Jinjin Xu, Dehong Hu, Yuehe Lin, Jinghong Li
Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1...
August 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28810752/rupturing-the-hemi-fission-intermediate-in-membrane-fission-under-tension-reaction-coordinates-kinetic-pathways-and-free-energy-barriers
#18
Guojie Zhang, Marcus Müller
Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin's constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i...
August 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28808969/methods-of-assessing-sting-activation-and-trafficking
#19
Vladislav Pokatayev, Nan Yan
The signaling adapter protein STING is crucial for the host immune response to cytosolic DNA and cyclic dinucleotides. Under basal conditions, STING resides on the endoplasmic reticulum (ER ) , but upon activation, it traffics through secretory pathway to cytoplasmic vesicles, where STING activates downstream immune signaling. Classical STING activation and trafficking are triggered by binding of cyclic dinucleotide ligands. STING signaling can also be activated by gain-of-function mutations that lead to constitutive trafficking of STING...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#20
Mads Eggert Nielsen, Gerd Jürgens, Hans Thordal-Christensen
Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for pre-invasive immunity; in post-invasive immunity the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against a non-adapted powdery mildew fungus (Blumeria graminis f...
August 14, 2017: Plant Cell
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