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Arp2/3

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https://www.readbyqxmd.com/read/28293874/diversity-of-actin-architecture-in-human-osteoclasts-network-of-curved-and-branched-actin-supporting-cell-shape-and-intercellular-micrometer-level-tubes
#1
Paula Pennanen, Maria Helena Alanne, Elnaz Fazeli, Takahiro Deguchi, Tuomas Näreoja, Sirkku Peltonen, Juha Peltonen
Osteoclasts are multinucleated bone-resorbing cells with a dynamic actin cytoskeleton. Osteoclasts are derived from circulating mononuclear precursors. Confocal and stimulated emission depletion (STED) super-resolution microscopy was used to investigate peripheral blood-derived human osteoclasts cultured on glass surfaces. STED and confocal microscopy demonstrated that the actin was curved and branched, for instance, in the vicinity of membrane ruffles. The overall architecture of the curved actin network extended from the podosomes to the top of the cell...
March 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28293092/clinicopathological-and-prognostic-significance-of-aberrant-arpin-expression-in-gastric-cancer
#2
Tao Li, Hong-Mei Zheng, Nai-Mei Deng, Ying-Jian Jiang, Jiang Wang, Dian-Liang Zhang
AIM: To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS: A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group...
February 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28255536/central-role-of-pi3k-syk-interaction-in-fibrinogen-induced-lamellipodia-and-filopodia-formation-in-platelets
#3
Raghvendra Singh
The WAVE complex-1, a complex of WAVE, Abi1, NAP1, PIR121, HSPC300, RacGTP and Arp2/3 proteins, and WASP complex-1, a complex of WASP, Cdc42, PIP2, and Arp2/3 proteins, are involved in lamellipodia and filopodia formation, respectively. It is known that the two complexes have opposite dynamics. Furthermore, Rac has two guanine nucleotide exchange factors, Vav and Sos, whose role in activating Rac is not well understood. In this work, by the construction of signaling network, analysis, and mathematical modeling, I show that Sos generates a pulse of WAVE complex-1, decreasing the response time of WAVE complex-1 formation upon the stimulation of platelets by fibrinogen...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28246120/kdm3a-coordinates-actin-dynamics-with-intraflagellar-transport-to-regulate-cilia-stability
#4
Patricia L Yeyati, Rachel Schiller, Girish Mali, Ioannis Kasioulis, Akane Kawamura, Ian R Adams, Christopher Playfoot, Nick Gilbert, Veronica van Heyningen, Jimi Wills, Alex von Kriegsheim, Andrew Finch, Juro Sakai, Christopher J Schofield, Ian J Jackson, Pleasantine Mill
Cilia assembly and disassembly are coupled to actin dynamics, ensuring a coherent cellular response during environmental change. How these processes are integrated remains undefined. The histone lysine demethylase KDM3A plays important roles in organismal homeostasis. Loss-of-function mouse models of Kdm3a phenocopy features associated with human ciliopathies, whereas human somatic mutations correlate with poor cancer prognosis. We demonstrate that absence of KDM3A facilitates ciliogenesis, but these resulting cilia have an abnormally wide range of axonemal lengths, delaying disassembly and accumulating intraflagellar transport (IFT) proteins...
February 28, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28238662/coordination-by-cdc42-of-actin-contractility-and-adhesion-for-melanoblast-movement-in-mouse-skin
#5
Emma F Woodham, Nikki R Paul, Benjamin Tyrrell, Heather J Spence, Karthic Swaminathan, Michelle R Scribner, Evangelos Giampazolias, Ann Hedley, William Clark, Frieda Kage, Daniel J Marston, Klaus M Hahn, Stephen W G Tait, Lionel Larue, Cord H Brakebusch, Robert H Insall, Laura M Machesky
The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin...
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28235780/inhibitory-cortactin-nanobodies-delineate-the-role-of-nta-and-sh3-domain-specific-functions-during-invadopodium-formation-and-cancer-cell-invasion
#6
Laurence Bertier, Ciska Boucherie, Olivier Zwaenepoel, Berlinda Vanloo, Marleen Van Troys, Isabel Van Audenhove, Jan Gettemans
Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain...
February 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28228548/contact-guidance-requires-spatial-control-of-leading-edge-protrusion
#7
G R Ramirez-San Juan, P W Oakes, M L Gardel
In vivo, geometric cues from the extra-cellular matrix (ECM) are critical for the regulation of cell shape, adhesion and migration. During contact guidance, the fibrillar architecture of the ECM promotes an elongated cell shape and migration along the fibrils. The subcellular mechanisms by which cells sense ECM geometry and translate it into changes in shape and migration direction, are not understood. Here, we pattern linear fibronectin features to mimic fibrillar ECM and elucidate the mechanisms of contact guidance...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28225074/the-wasp-arp2-3-complex-signal-cascade-is-involved-in-actin-dependent-sperm-nuclei-migration-during-double-fertilization-in-tobacco-and-maize
#8
Xiongbo Peng, Tingting Yan, Mengxiang Sun
Sperm nuclear migration during fertilization in Arabidopsis and rice has recently been found to be actin-dependent, but the driving force behind this actin cytoskeleton-dependent motion is unclear. Here, we confirmed that the actin-dependent sperm nuclei migration during fertilization is a conserved mechanism in plants. Using in vitro fertilization systems, we showed that a functional actin is also essential in maize and tobacco for sperm nuclei migration after gamete membrane fusion. Cytoskeleton depolymerization inhibitor treatments supported the view that sperm nuclei migration is actin-dependent but microtubule-independent in both egg cell and central cell during double fertilization...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218453/divergent-roles-of-%C3%AE-and-%C3%AE-actin-isoforms-during-spread-of-vaccinia-virus
#9
N Bishara Marzook, Sharissa L Latham, Helena Lynn, Christopher Mckenzie, Christine Chaponnier, Georges E Grau, Timothy P Newsome
Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Here we show that virus-tipped actin comets are composed of β- and γ-actin. We employed isoform-specific siRNA knockdown to examine the role of the two isoforms in VACV-induced actin comets...
February 20, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28194011/self-organizing-actin-patterns-shape-membrane-architecture-but-not-cell-mechanics
#10
M Fritzsche, D Li, H Colin-York, V T Chang, E Moeendarbary, J H Felce, E Sezgin, G Charras, E Betzig, C Eggeling
Cell-free studies have demonstrated how collective action of actin-associated proteins can organize actin filaments into dynamic patterns, such as vortices, asters and stars. Using complementary microscopic techniques, we here show evidence of such self-organization of the actin cortex in living HeLa cells. During cell adhesion, an active multistage process naturally leads to pattern transitions from actin vortices over stars into asters. This process is primarily driven by Arp2/3 complex nucleation, but not by myosin motors, which is in contrast to what has been theoretically predicted and observed in vitro...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28186323/the-arp2-3-inhibitory-protein-arpin-is-dispensable-for-chemotaxis
#11
Irène Dang, Joern Linkner, Jun Yan, Daniel Irimia, Jan Faix, Alexis Gautreau
Arpin is an Arp2/3 inhibitory protein, which decreases the protrusion lifetime and hence directional persistence in the migration of diverse cells. Arpin is activated by the small GTPase Rac, which controls cell protrusion, thus closing a negative feedback loop that renders the protrusion intrinsically unstable. Because of these properties, it was proposed that Arpin might play a role in directed migration, where directional persistence has to be fine-tuned. We report here, however, that Arpin depleted tumor cells and Arpin knock-out Dictyostelium amoeba display no obvious defect in chemotaxis...
February 10, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28161632/mammalian-verprolin-cr16-acts-as-a-modulator-of-itsn-scaffold-proteins-association-with-actin
#12
Sergii Kropyvko, Tetyana Gryaznova, Dmytro Morderer, Alla Rynditch
Actin cytoskeleton rearrangements are required for normal cell functioning, and their deregulation leads to various pathologies. Members of two mammalian protein families - ITSNs (ITSN1 and ITSN2) and verprolins (WIP, CR16 and WIRE) are involved in Cdc42/N-WASP/Arp2/3 signaling pathway-mediated remodeling of the actin cytoskeleton. Recently we demonstrated that ITSNs interact with the actin-regulating protein WIP. Here, we show that other member of verprolin family, CR16, also forms complexes with ITSN1 and ITSN2 in human cell lines...
February 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28154159/the-t-cell-ift20-interactome-reveals-new-players-in-immune-synapse-assembly
#13
Donatella Galgano, Anna Onnis, Elisa Pappalardo, Federico Galvagni, Oreste Acuto, Cosima T Baldari
Sustained signalling at the immune synapse (IS) requires the synaptic delivery of recycling endosome-associated TCRs. IFT20, a component of the intraflagellar transport system, controls TCR recycling to the IS as a complex with IFT57 and IFT88. Here, we used quantitative mass spectrometry to identify additional interaction partners of IFT20 in Jurkat T cells. In addition to IFT57 and IFT88, the analysis revealed new binding partners, including IFT54, GMAP-210, Arp2/3 complex subunit-3 (ARPC3), COP9 signalosome subunit-1 (CSN1), and ERGIC-53...
February 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28128308/%C3%AE-v-class-integrins-exert-dual-roles-on-%C3%AE-5%C3%AE-1-integrins-to-strengthen-adhesion-to-fibronectin
#14
Mitasha Bharadwaj, Nico Strohmeyer, Georgina P Colo, Jonne Helenius, Niko Beerenwinkel, Herbert B Schiller, Reinhard Fässler, Daniel J Müller
Upon binding to the extracellular matrix protein, fibronectin, αV-class and α5β1 integrins trigger the recruitment of large protein assemblies and strengthen cell adhesion. Both integrin classes have been functionally specified, however their specific roles in immediate phases of cell attachment remain uncharacterized. Here, we quantify the adhesion of αV-class and/or α5β1 integrins expressing fibroblasts initiating attachment to fibronectin (≤120 s) by single-cell force spectroscopy. Our data reveals that αV-class integrins outcompete α5β1 integrins...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28115704/wave1-in-neurons-expressing-the-d1-dopamine-receptor-regulates-cellular-and-behavioral-actions-of-cocaine
#15
Ilaria Ceglia, Ko-Woon Lee, Michael E Cahill, Steven M Graves, David Dietz, Dalton J Surmeier, Eric J Nestler, Angus C Nairn, Paul Greengard, Yong Kim
Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) complex-mediated actin polymerization. Our previous studies have found WAVE1 to be inhibited by Cdk5-mediated phosphorylation in brain and to play a role in the regulation of dendritic spine morphology. Here we report that mice in which WAVE1 was knocked out (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but not mice where WAVE1 was knocked out in neurons expressing the D2 dopamine receptor (D2-KO), exhibited a significant decrease in place preference associated with cocaine...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28106075/phosphatidylinositol-3-4-bisphosphate-regulates-neurite-initiation-and-dendrite-morphogenesis-via-actin-aggregation
#16
Shu-Xin Zhang, Li-Hui Duan, Shun-Ji He, Gui-Feng Zhuang, Xiang Yu
Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation. Here we demonstrate that local clustering of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), a phospholipid with relatively few known signaling functions, is necessary and sufficient for aggregating actin and promoting neuritogenesis...
February 2017: Cell Research
https://www.readbyqxmd.com/read/28059163/phosphoproteomic-comparison-of-pik3ca-and-pten-signalling-identifies-the-nucleotidase-nt5c-as-a-novel-akt-substrate
#17
Larissa S Moniz, Silvia Surinova, Essam Ghazaly, Lorena Gonzalez Velasco, Syed Haider, Juan Carlos Rodríguez-Prados, Inma M Berenjeno, Claude Chelala, Bart Vanhaesebroeck
To identify novel effectors and processes regulated by PI3K pathway activation, we performed an unbiased phosphoproteomic screen comparing two common events of PI3K deregulation in cancer: oncogenic Pik3ca mutation (Pik3ca(H1047R)) and deletion of Pten. Using mouse embryonic fibroblast (MEF) models that generate inducible, low-level pathway activation as observed in cancer, we quantified 7566 unique phosphopeptides from 3279 proteins. A number of proteins were found to be differentially-regulated by Pik3ca(H1047R) and Pten loss, suggesting unique roles for these two events in processes such as vesicular trafficking, DNA damage repair and RNA splicing...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28013022/nano-scale-actin-network-characterization-of-fibroblast-cells-lacking-functional-arp2-3-complex
#18
Karen L Anderson, Christopher Page, Mark F Swift, Praveen Suraneni, Mandy E W Janssen, Thomas D Pollard, Rong Li, Niels Volkmann, Dorit Hanein
Arp2/3 complex is thought to be the primary protrusive force generator in cell migration by controlling the assembly and turnover of the branched filament network that pushes the leading edge of moving cells forward. However, mouse fibroblasts without functional Arp2/3 complex migrate at rates similar to wild-type cells, contradicting this paradigm. We show by correlative fluorescence and large-scale cryo-tomography studies combined with automated actin-network analysis that the absence of functional Arp2/3 complex has profound effects on the nano-scale architecture of actin networks...
March 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/27998771/deficiency-in-ubiquitin-like-protein-ubl4a-impairs-migration-of-fibroblasts-and-macrophages
#19
Yu Zhao, Huaiyuan Zhang, Carlos Affonso, Raiza Bonomo, Adriana Mañas, Jialing Xiang
Ubiquitin-like protein Ubl4A is a small, multi-functional protein with no ubiquitination activity. We have previously demonstrated that Ubl4A directly interacts with actin-related protein 2/3 complex (Arp2/3) and promotes Arp2/3-dependent actin branching, thereby accelerating plasma membrane translocation of protein kinase Akt upon insulin stimulation. Here, we show that Ubl4A is critical for plasma membrane protrusion and cell migration. Ubl4A, F-actin and Arp2/3 are co-localized at the cell leading edges during wound closure...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27998058/label-free-neuroproteomics-of-the-hippocampal-accumbal-circuit-reveals-deficits-in-neurotransmitter-and-neuropeptide-signaling-in-mice-lacking-ethanol-sensitive-adenosine-transporter
#20
Alfredo Oliveros, Phillip Starski, Daniel Lindberg, Sun Choi, Carrie J Heppelmann, Surendra Dasari, Doo-Sup Choi
The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1(-/-)) in mice. Here we perform quantitative LC-MS/MS neuroproteomics in the dHip and NAc of ENT1(-/-) mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis)...
February 27, 2017: Journal of Proteome Research
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