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https://www.readbyqxmd.com/read/29785947/-n-wasp-regulates-cortical-neuron-migration-through-its-polypro-and-vca-domains
#1
Xiu Lian Shen, Yi Chao Lu, Zhi Lian Jia, Qiang Wu
Cortical neuron migration in the developing mouse forebrain is a complex process, which contains several steps related to cytoskeleton dynamics and remodeling. Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP-WAVE family, regulates actin cytoskeleton reorganization through the binding of its VCA domain to the Arp2/3 complex. Here we report expression patterns of N-WASP gene in the mouse developing embryonic cortex (E12.5~ E18.5) and find its expression levels are decreased during embryonic development...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29779865/gmf-as-an-actin-network-remodeling-factor
#2
REVIEW
Bruce L Goode, Meredith O Sweeney, Julian A Eskin
Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex...
May 18, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29774203/small-rho-gtpases-and-the-effector-vipa-mediate-the-invasion-of-epithelial-cells-by-filamentous-legionella-pneumophila
#3
Akriti Prashar, María Eugenia Ortiz, Stefanie Lucarelli, Elizabeth Barker, Zohreh Tabatabeiyazdi, Feras Shamoun, Deepa Raju, Costin Antonescu, Cyril Guyard, Mauricio R Terebiznik
Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates β1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#4
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29743604/small-gtpases-and-bar-domain-proteins-regulate-branched-actin-polymerisation-for-clathrin-and-dynamin-independent-endocytosis
#5
Mugdha Sathe, Gayatri Muthukrishnan, James Rae, Andrea Disanza, Mukund Thattai, Giorgio Scita, Robert G Parton, Satyajit Mayor
Using real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42 which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected. Removal of IRSp53, a negative curvature sensing protein, abolishes CG endocytosis...
May 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29731300/actin-cross-linking-toxin-is-a-universal-inhibitor-of-tandem-organized-and-oligomeric-g-actin-binding-proteins
#6
Elena Kudryashova, David B Heisler, Blake Williams, Alyssa J Harker, Kyle Shafer, Margot E Quinlan, David R Kovar, Dimitrios Vavylonis, Dmitri S Kudryashov
Delivery of bacterial toxins to host cells is hindered by host protective barriers. This obstruction dictates a remarkable efficiency of toxins, a single copy of which may kill a host cell. Efficiency of actin-targeting toxins is further hampered by an overwhelming abundance of their target. The actin cross-linking domain (ACD) toxins of Vibrio species and related bacterial genera catalyze the formation of covalently cross-linked actin oligomers. Recently, we reported that the ACD toxicity can be amplified via a multivalent inhibitory association of actin oligomers with actin assembly factors formins, suggesting that the oligomers may act as secondary toxins...
April 21, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29717064/glycerol-monolaurate-induces-filopodia-formation-by-disrupting-the-association-between-lat-and-slp-76-microclusters
#7
Michael S Zhang, Phuong M Tran, Alexander J Wolff, Mikaela M Tremblay, Micaela G Fosdick, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)-induced signaling and T cell effector function. Actin rearrangement is needed for the interaction of T cells with antigen-presenting cells and for migration to sites of infection. Because of the critical role actin rearrangement plays in T cell effector function, we analyzed the effect of GML on the rearrangement of the actin cytoskeleton after TCR activation. We found that GML-treated human T cells were less adherent than untreated T cells and did not form actin ring structures but instead developed numerous inappropriate actin-mediated filopodia...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29703977/deconvolution-of-subcellular-protrusion-heterogeneity-and-the-underlying-actin-regulator-dynamics-from-live-cell-imaging
#8
Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee
Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29700112/rhoa-rac1-and-cdc42-differentially-regulate-asma-and-collagen-i-expression-in-mesenchymal-stem-cells
#9
Jianfeng Ge, Laurent Burnier, Maria Adamopoulou, Mei Qi Kwa, Matthias Schaks, Klemens Rottner, Cord Brakebusch
Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29691404/capping-protein-controlled-actin-polymerization-shapes-lipid-membranes
#10
Katharina Dürre, Felix C Keber, Philip Bleicher, Fridtjof Brauns, Christian J Cyron, Jan Faix, Andreas R Bausch
Arp2/3 complex-mediated actin assembly at cell membranes drives the formation of protrusions or endocytic vesicles. To identify the mechanism by which different membrane deformations can be achieved, we reconstitute the basic membrane deformation modes of inward and outward bending in a confined geometry by encapsulating a minimal set of cytoskeletal proteins into giant unilamellar vesicles. Formation of membrane protrusions is favoured at low capping protein (CP) concentrations, whereas the formation of negatively bent domains is promoted at high CP concentrations...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29678956/local-actin-polymerization-during-endocytic-carrier-formation
#11
REVIEW
Claudia Hinze, Emmanuel Boucrot
Extracellular macromolecules, pathogens and cell surface proteins rely on endocytosis to enter cells. Key steps of endocytic carrier formation are cargo molecule selection, plasma membrane folding and detachment from the cell surface. While dedicated proteins mediate each step, the actin cytoskeleton contributes to all. However, its role can be indirect to the actual molecular events driving endocytosis. Here, we review our understanding of the molecular steps mediating local actin polymerization during the formation of endocytic carriers...
April 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29668757/actin-polymerization-in-the-endosomal-pathway-but-not-on-the-coxiella-containing-vacuole-is-essential-for-pathogen-growth
#12
Heather E Miller, Charles L Larson, Robert A Heinzen
Coxiella burnetii is an intracellular bacterium that replicates within an expansive phagolysosome-like vacuole. Fusion between the Coxiella-containing vacuole (CCV) and late endosomes/multivesicular bodies requires Rab7, the HOPS tethering complex, and SNARE proteins, with actin also speculated to play a role. Here, we investigated the importance of actin in CCV fusion. Filamentous actin patches formed around the CCV membrane that were preferred sites of vesicular fusion. Accordingly, the mediators of endolysosomal fusion Rab7, VAMP7, and syntaxin 8 were concentrated in CCV actin patches...
April 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29668357/formin-dependent-tgf-%C3%AE-signaling-for-epithelial-to-mesenchymal-transition
#13
Manish K Rana, Francesca M Aloisio, Changhoon Choi, Diane L Barber
The role of distinct actin filaments architectures in epithelial plasticity remains incompletely understood. We, therefore, determined roles for formins and the Arp2/3 complex, which are actin nucleators generating unbranched and branched actin filaments, respectively, in the process of epithelial to mesenchymal transition (EMT). In clonal lung, mammary and renal epithelial cells, the formin activity inhibitor SMIFH2 but not the Arp2/3 complex activity inhibitor CK666 blocked EMT induced by TGF-β. SMIFH2 prevented the proximal signal of increased Smad2 phosphorylation, and hence also blocked downstream EMT markers, including actin filament remodeling, decreased expression of the adherens junction protein E-cadherin and increased expression of the matrix protein fibronectin and the transcription factor Snail...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29643414/switching-between-individual-and-collective-motility-in-b-lymphocytes-is-controlled-by-cell-matrix-adhesion-and-inter-cellular-interactions
#14
Javier Rey-Barroso, Daniel S Calovi, Maud Combe, Yolla German, Mathieu Moreau, Astrid Canivet, Xiaobo Wang, Clément Sire, Guy Theraulaz, Loïc Dupré
Lymphocytes alternate between phases of individual migration across tissues and phases of clustering during activation and function. The range of lymphocyte motility behaviors and the identity of the factors that govern them remain elusive. To explore this point, we here collected unprecedented statistics pertaining to cell displacements, cell:matrix and cell:cell interactions using a model B cell line as well as primary human B lymphocytes. At low cell density, individual B lymphocytes displayed a high heterogeneity in their speed and diffusivity...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615809/tagln2-polymerizes-g-actin-in-a-low-ionic-state-but-blocks-arp2-3-nucleated-actin-branching-in-physiological-conditions
#15
Hye-Ran Kim, Min-Sung Kwon, Sangmin Lee, YeVin Mun, Kyung-Sik Lee, Chang-Hyun Kim, Bo-Ra Na, Bit Na Rae Kim, Indre Piragyte, Hyun-Su Lee, Youngsoo Jun, Mi Sun Jin, Young-Min Hyun, Hyun Suk Jung, Ji Young Mun, Chang-Duk Jun
TAGLN is an actin-binding protein family that comprises three isoforms with theorized roles in smooth muscle differentiation, tumour development, lymphocyte activation, and brain chemistry. However, their fundamental characteristics in regulation of the actin-based cytoskeleton are not fully understood. Here we show that TAGLN2 (including TAGLN1 and TAGLN3) extensively nucleates G-actin polymerization under low-salt conditions, where polymerization would be completely suppressed. The calponin homology domain and actin-binding loop are essential to mechanically connect two adjacent G-actins, thereby mediating multimeric interactions...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29602811/identification-of-proteins-required-for-precise-positioning-of-apc2-in-dendrites
#16
Alexis T Weiner, Dylan Y Seebold, Nick L Michael, Michelle Guignet, Chengye Feng, Brandon Follick, Brandon A Yusko, Nathan P Wasilko, Pedro Torres-Gutierrez, Melissa M Rolls
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points...
March 30, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29593429/upregulation-of-arp2-expression-is-associated-with-the-prognosis-and-prediction-of-lymph-node-metastasis-in-bladder-urothelial-carcinoma
#17
Ning Xu, Gen-Yi Qu, Yu-Peng Wu, Xiao-Dong Li, Min-Yi Lin, Shao-Hao Chen, Xue-Yi Xue, Yong Wei
Objective: Upregulation of actin-related protein 2/3 complex subunit 2 (Arp2) is observed in various tumors, but its expression pattern has not been revealed in bladder urothelial carcinoma (BUC). The purpose of this study was to investigate the role of Arp2 expression in the pathological features and the prognosis as well as lymph node metastasis of BUC. Methods: A total of 228 tissue specimens from BUC patients who underwent a radical cystectomy were collected...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29587415/the-sealing-zone-in-osteoclasts-a-self-organized-structure-on-the-bone
#18
REVIEW
Jiro Takito, Satoshi Inoue, Masanori Nakamura
Osteoclasts form a specialized cell-matrix adhesion structure, known as the "sealing zone", during bone resorption. The sealing zone is a dynamic actin-rich structure that defines the resorption area of the bone. The detailed dynamics and fine structure of the sealing zone have been elusive. Osteoclasts plated on glass do not form a sealing zone, but generate a separate supra-molecular structure called the "podosome belt". Podosomes are integrin-based adhesion complexes involved in matrix adhesion, cell migration, matrix degradation, and mechanosensing...
March 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29581253/naa80-is-actin-s-n-terminal-acetyltransferase-and-regulates-cytoskeleton-assembly-and-cell-motility
#19
Adrian Drazic, Henriette Aksnes, Michaël Marie, Malgorzata Boczkowska, Sylvia Varland, Evy Timmerman, Håvard Foyn, Nina Glomnes, Grzegorz Rebowski, Francis Impens, Kris Gevaert, Roberto Dominguez, Thomas Arnesen
Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and filamentous forms, a process exquisitely regulated in cells by a large number of actin-binding and signaling proteins. Additionally, several posttranslational modifications control the cellular functions of actin, including most notably N-terminal (Nt)-acetylation, a prevalent modification throughout the animal kingdom...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29567535/nanobodies-targeting-cortactin-proline-rich-helical-and-actin-binding-regions-downregulate-invadopodium-formation-and-matrix-degradation-in-scc-61-cancer-cells
#20
Laurence Bertier, Tim Hebbrecht, Elien Mettepenningen, Natasja De Wit, Olivier Zwaenepoel, Adriaan Verhelle, Jan Gettemans
Cortactin is a multidomain actin binding protein that activates Arp2/3 mediated branched actin polymerization. This is essential for the formation of protrusive structures during cancer cell invasion. Invadopodia are cancer cell-specific membrane protrusions, specialized at extracellular matrix degradation and essential for invasion and tumor metastasis. Given the unequivocal role of cortactin at every stage of invadopodium formation, it is considered an invadopodium marker and potential drug target. We used cortactin nanobodies to examine the role of cortactin domain-specific function at endogenous protein level...
March 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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