Similar Datasets
Project description:Tumour-derived microvesicles (TMVs) comprise a class of extracellular vesicles released from tumour cells that are now understood to facilitate communication between the tumour and the surrounding microenvironment. Despite their significance, the regulatory mechanisms governing the trafficking of bioactive cargos to TMVs at the cell surface remain poorly defined. Here we describe a molecular pathway for the delivery of microRNA (miRNA) cargo to nascent TMVs involving the dissociation of a pre-miRNA/Exportin-5 complex from Ran-GTP following nuclear export and its subsequent transfer to a cytoplasmic shuttle comprised of ARF6-GTP and GRP1. As such, ARF6 activation increases the pre-miRNA cargo contained within TMVs through a process that requires the casein kinase 2-mediated phosphorylation of RanGAP1. Furthermore, TMVs were found to contain pre-miRNA processing machinery including Dicer and Argonaute-2, which allow for cell-free pre-miRNA processing within shed vesicles. These findings offer cellular targets to block the loading and processing of pre-miRNAs within TMVs.
| S-EPMC6697424 | biostudies-literature
Project description:An ARF6-Exportin-5 Axis Delivers pre-miRNA Cargo to Tumor Microvesicles.
| PRJNA535491 | ENA
Project description:The aim of this study was to examine the roles of Auxin Response Factors (ARFs) in flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were treated with 10 uM indole-3-acetic acid for thirty minutes to identify genes that respond rapidly to auxin in an ARF6/ARF8-dependent manner. Keywords: auxin response; comparison of wild type and arf6 arf8 mutants
2005-06-30 | GSE2847 | GEO
Project description:The aim of this study was to examine the contribution of ARF6 and ARF8 to flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Flowers from wild-type, arf6/arf6 ARF8/arf8, and arf6 arf8 plants were separated into stage 1-10 flowers, stage 11+12 flowers, and stage 13-14 flowers to define the developmental stages at which ARF6 and ARF8 are required for gene expression.
2007-06-28 | E-GEOD-2848 | biostudies-arrayexpress
Project description:Arf6 is a small GTPase regulating many cellular processes including cytoskeletal remodeling, receptor endocytosis, and phagocytosis of pathogens. Arf6 knockdown in neutrophil (PMN)-like cells was reported to inhibit chemotactic peptide-mediated activation of phospholipase D, the oxidative burst, and 2 integrin-dependent adhesion. In mice, the migration of PMNs knock out for Arf6 to the site of inflammation was diminished and associated with reduced cell surface expression of 2 integrins. Conditional knockout mice lacking Arf6 in PMNs were used to assess the impact of Arf6 depletion on the functions and gene expression profile of PMNs isolated from the mouse air pouch injected with lipopolysaccharide (LPS). The expression of several genes was modulated in PMNs-Arf6 cKO with Lpar6 and Lacc-1 being the most up-regulated and down-regulated genes, respectively. Decreased expressed of Lacc-1 was validated at the protein level in PMN-Arf6 cKO, and silencing of Arf6 in THP-1 monocytic cells delayed LPS-mediated Lacc-1 expression. Here we report that fMLP or zymosan-induced glycolysis and oxygen consumption rate were decreased in air pouch PMNs but not in BM PMNs of Arf6 cKO mice when compared to control floxed cells. Reduced oxygen consumption correlated with decreased production of superoxide and ROS. Depletion of Arf6 in mouse PMNs also reduced phagocytosis and interfered apoptosis. The data suggest that Arf6 regulates energy metabolism, which may contribute to impaired phagocytosis, ROS production, and apoptosis in PMN-Arf6 cKO. This study provides new information on the functions and the inflammatory pathways influenced by Arf6 in PMNs.
2021-05-28 | GSE151436 | GEO
Project description:The aim of this study was to examine the roles of Auxin Response Factors (ARFs) in flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were treated with 10 uM indole-3-acetic acid for thirty minutes to identify genes that respond rapidly to auxin in an ARF6/ARF8-dependent manner. Experiment Overall Design: Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were sprayed with 10 mM indole-3-acetic acid in 1% methanol, 0.05% Tween-20. Thirty minutes after treatment, flowers (stage 1-14) were collected, frozen in liquid nitrogen, and used for RNA extraction.
2007-07-11 | E-GEOD-2847 | biostudies-arrayexpress
Project description:Recent studies reported contradictory results regarding the role of ADP-ribosylation factor 6 (ARF6), a small GTPase known to regulate actin cytoskeleton, in dendritic spine development and maintenance. We readdress this question, and found that ARF6 either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation facilitates filopodia to spines transition, increasing the spine formation in developing neurons while it decreases spine density in matured neurons. Consistently, genome-wide microarray analysis revealed that Arf6 activation in developing and matured neurons leads to opposite expression patterns of a subset of genes that are involved in neuronal morphology.
2015-04-02 | GSE40937 | GEO
Project description:The biogenesis and function of mature microRNAs (miRNAs) is dependent on the nuclear export of miRNA precursors (pre-miRNA) by Exportin-5 (Exp5). To characterize the molecular mechanisms of how pre-miRNA is recognized and transported by Exp5, we have performed 21 molecular dynamic (MD) simulations of RNA-bound Exp5 (Exp5-RanGTP-premiRNA, Exp5-RanGDP-premiRNA, Exp5-premiRNA), RNA-unbound Exp5 (Exp5-RanGTP, Exp5-RanGDP, apo-Exp5), and pre-miRNA. Our simulations with standard MD, steered molecular dynamics (SMD), and energy analysis have shown that (1) Free Exp5 undergoes extensive opening motion, and in this way facilitates the RanGTP binding. (2) RanGTP efficiently regulates the association/dissociation of pre-miRNA to its complex by inducing conformational changes in the HEAT-repeat helix stacking of Exp5. (3) The GTP hydrolysis prevents Ran from rebinding to Exp5 by regulating the hydrophobic interfaces and salt bridges between Ran and Exp5. (4) The transition from the A'-form to the A-form of the pre-miRNA modulates the structural complementarities between the protein and the pre-miRNA, thus promoting efficient assembly of the complex. (5) The base-flipping process (from the closed to the fully flipped state) of the 2-nt 3' overhang is a prerequisite for the pre-miRNA recognition by Exp5, which occurs in a sequence-independent manner as evidenced by the fact that different 2-nt 3' overhangs bind to Exp5 in essentially the same way. And finally, a plausible mechanism of the pre-miRNA export cycle has been proposed explaining how the protein-protein and protein-RNA interactions are coordinated in physiological conditions.
| S-EPMC3153975 | biostudies-literature
Project description:Autophagic and endosomal dysfunctions are prominently observed at preclinical stages of Alzheimer's disease (AD) as well as in presenilin (PSEN) 1-deficient mice and neurons. In the latter, the defects relate to the γ-secretase-independent role of PSEN in lysosomal fusion and organelle turnover. While we demonstrated previously that the impaired capacity of lysosomal fusion is associated with a significant reduction in lysosomal calcium storage/release, the underlying mechanism remained unexplored. Here we demonstrate that PSEN-deficient cells are impaired in endosomal recycling of several cargo proteins reminiscent of clathrin-independent carriers and lipid rafts. This is accompanied by the accumulation of cholesterol in LAMP1-positive organelles. The small GTPase ARF6, an important regulator of lipid raft recycling, fully rescues the endo-lysosomal abnormalities in PSEN-/- cells, suggesting that defective recycling is upstream of lysosomal dysfunction. PSEN-/- cells and neurons present significantly reduced ARF6 expression levels. Importantly, similar decreased ARF6 levels are observed in aging murine neurons and brain and are even more pronounced in AD brains, suggesting a particular vulnerability of ARF6-mediated recycling in the early etiology of AD.
2017-12-15 | GSE44454 | GEO
Project description:Metastasis is responsible for nearly 90% of all cancer-related deaths. Despite global efforts to prevent aggressive tumours, cancers such as pancreatic ductal adenocarcinoma (PDAC) are poorly diagnosed in the primary stage, resulting in lethal metastatic disease. RAS mutations are known to promote tumour spread, with mutant KRAS present in almost 90% of cases. Until recently, mutant KRAS remained untargeted and, despite the recent development of inhibitors, results show that tumour cells develop resistance. Another strategy for targeting mutant KRAS-dependent PDAC metastasis may come from targeting the downstream effectors of KRAS. One such axis, which controls tumour proliferation, invasiveness and immune evasion, is represented by ARF6-ASAP1. Here we show that targeting ARF6 results in adaptive rewiring that can restore proliferation and invasion potential over time. Using time-series RNA and ATAC sequencing approaches, we identified TLR-dependent NFκB, TNFα and hypoxia signalling as key drivers of adaptation in ARF6-depleted KRAS-dependent PDAC. Using in vitro and in vivo assays, we show that knocking down TLR2 with ARF6 significantly reduces proliferation, migration and invasion. Taken together, our data shed light on a novel co-targeting strategy with the therapeutic potential to counteract PDAC proliferation and metastasis.
2023-12-02 | GSE247513 | GEO