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https://www.readbyqxmd.com/read/28333264/single-cell-transcriptomics-mega-phylogeny-and-the-genetic-basis-of-morphological-innovations-in-rhizaria
#1
Anders K Krabberød, Russell J S Orr, Jon Bråte, Tom Kristensen, Kjell R Bjørklund, Kamran Shalchian-Tabrizi
The innovation of the eukaryote cytoskeleton enabled phagocytosis, intracellular transport and cytokinesis, and is responsible for the diversity of eukaryotic morphologies. Still, the relationship between phenotypic innovations in the cytoskeleton and their underlying genotype is poorly understood. To explore the genetic mechanism of morphological evolution of the eukaryotic cytoskeleton we provide the first single cell transcriptomes from uncultured, free-living unicellular eukaryotes: the polycystine radiolarian Lithomelissa setosa (Nassellaria) and Sticholonche zanclea (Taxopodida)...
March 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28332566/a-conformational-change-within-the-wave2-complex-regulates-its-degradation-following-cellular-activation
#2
Noah Joseph, Guy Biber, Sophia Fried, Barak Reicher, Omer Levy, Batel Sabag, Elad Noy, Mira Barda-Saad
WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331069/efficiency-of-lamellipodia-protrusion-is-determined-by-the-extent-of-cytosolic-actin-assembly
#3
Georgi Dimchev, Anika Steffen, Frieda Kage, Vanessa Dimchev, Julien Pernier, Marie-France Carlier, Klemens Rottner
Cell migration and cell-cell communication involves the protrusion of actin-rich cell surface projections such as lamellipodia and filopodia. Lamellipodia are networks of actin filaments generated and turned over by filament branching through Arp2/3 complex. Inhibition of branching is commonly agreed to eliminate formation and maintenance of lamellipodial actin networks, but the regulation of nucleation or elongation of Arp2/3-independent filament populations within the network e.g. by formins or Ena/VASP family members and its impact on the effectivity of protrusion have remained unclear...
March 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28327544/fmnl-formins-boost-lamellipodial-force-generation
#4
Frieda Kage, Moritz Winterhoff, Vanessa Dimchev, Jan Mueller, Tobias Thalheim, Anika Freise, Stefan Brühmann, Jana Kollasser, Jennifer Block, Georgi Dimchev, Matthias Geyer, Hans-Joachim Schnittler, Cord Brakebusch, Theresia E B Stradal, Marie-France Carlier, Michael Sixt, Josef Käs, Jan Faix, Klemens Rottner
Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation...
March 22, 2017: Nature Communications
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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