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https://www.readbyqxmd.com/read/29339159/analysis-of-the-interactions-between-gmf-and-arp2-3-complex-in-two-binding-sites-by-molecular-dynamics-simulation
#1
A Popinako, M Antonov, D Dibrova, A Chemeris, O S Sokolova
The Arp2/3 complex plays a key role in nucleating actin filaments branching. The glia maturation factor (GMF) competes with activators for interacting with the Arp2/3 complex and initiates the debranching of actin filaments. In this study, we performed a comparative analysis of interactions between GMF and the Arp2/3 complex and identified new amino acid residues involved in GMF binding to the Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM techniques. Using molecular dynamics simulations we demonstrated the quantitative and qualitative changes in hydrogen bonds upon binding with GMF...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335527/myosin-va-is-required-for-preciliary-vesicle-transportation-to-the-mother-centriole-during-ciliogenesis
#2
Chien-Ting Wu, Hsin-Yi Chen, Tang K Tang
Primary cilia play essential roles in signal transduction and development. The docking of preciliary vesicles at the distal appendages of a mother centriole is an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here, we demonstrate that myosin-Va mediates the transportation of preciliary vesicles to the mother centriole and reveal the underlying mechanism. We also show that the myosin-Va-mediated transportation of preciliary vesicles is the earliest event that defines the onset of ciliogenesis...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29328918/transmembrane-pickets-connect-cyto-and-pericellular-skeletons-forming-barriers-to-receptor-engagement
#3
Spencer A Freeman, Anthony Vega, Magdalena Riedl, Richard F Collins, Phillip P Ostrowski, Elliot C Woods, Carolyn R Bertozzi, Markku I Tammi, Diane S Lidke, Pauline Johnson, Satyajit Mayor, Khuloud Jaqaman, Sergio Grinstein
Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins ("pickets") that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29288926/efhd2-swiprosin-1-regulates-lps-induced-macrophage-recruitment-via-enhancing-actin-polymerization-and-cell-migration
#4
Ye Tu, Lichao Zhang, Lingchang Tong, Yue Wang, Su Zhang, Rongmei Wang, Ling Li, Zhibin Wang
Macrophage motility is vital in innate immunity, which contributes strategically to the defensive inflammation process. During bacterial infection, lipopolysaccharide (LPS) potently activates the migration of macrophages via the NF-κB/iNOS/c-Src signaling pathway. However, the downstream region of c-Src that participates in macrophage migration is unclear. EFhd2, a novel actin bundling protein, was evaluated for its role in LPS-stimulated macrophage migration in this study. We found that LPS stimulated the up-regulation, tyrosine phosphorylation and membrane translocation of EFhd2 in macrophages...
December 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29223862/wave-regulates-cadherin-junction-assembly-and-turnover-during-epithelial-polarization
#5
Shashikala Sasidharan, Sofya Borinskaya, Falshruti Patel, Yelena Bernadskaya, Sailaja Mandalapu, Maria Agapito, Martha Soto
Actin is an integral component of epithelial apical junctions, yet the interactions of branched actin regulators with apical junction components are still not clear. Biochemical data have shown that α-catenin inhibits Arp2/3-dependent branched actin. These results suggested that branched actin is only needed at earliest stages of apical junction development. We use live imaging in developing C. elegans embryos to test models for how WAVE-induced branched actin collaborates with other apical junction proteins during the essential process of junction formation and maturation...
December 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29212877/high-speed-super-resolution-imaging-of-the-proteins-in-fission-yeast-clathrin-mediated-endocytic-actin-patches
#6
Rajesh Arasada, Wasim A Sayyad, Julien Berro, Thomas D Pollard
To internalize nutrients and cell surface receptors via clathrin mediated endocytosis cells assemble at least 50 proteins including clathrin, clathrin-interacting proteins, actin filaments and actin binding proteins in a highly ordered and regulated fashion. The molecular mechanism by which actin filament polymerization deforms the cell membrane is unknown, largely due to lack of knowledge about the organization of the regulatory proteins and actin filaments. We used high-speed super-resolution localization microscopy (FPALM) of live fission yeast cells to improve the spatial resolution to ∼35 nm with 1 s temporal resolution...
December 6, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29212790/the-arp2-3-regulatory-system-and-its-deregulation-in-cancer
#7
REVIEW
Nicolas Molinie, Alexis Gautreau
The Arp2/3 complex is an evolutionary conserved molecular machine that generates branched actin networks. When activated, the Arp2/3 complex contributes the actin branched junction and thus cross-links the polymerizing actin filaments in a network that exerts a pushing force. The different activators initiate branched actin networks at the cytosolic surface of different cellular membranes to promote their protrusion, movement, or scission in cell migration and membrane traffic. Here we review the structure, function, and regulation of all the direct regulators of the Arp2/3 complex that induce or inhibit the initiation of a branched actin network and that controls the stability of its branched junctions...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29212018/structure-and-function-of-an-actin-based-filter-in-the-proximal-axon
#8
Varuzhan Balasanyan, Kaori Watanabe, William P Dempsey, Tommy L Lewis, Le A Trinh, Don B Arnold
The essential organization of microtubules within neurons has been described; however, less is known about how neuronal actin is arranged and the functional implications of its arrangement. Here, we describe, in live cells, an actin-based structure in the proximal axon that selectively prevents some proteins from entering the axon while allowing the passage of others. Concentrated patches of actin in proximal axons are present shortly after axonal specification in rat and zebrafish neurons imaged live, and they mark positions where anterogradely traveling vesicles carrying dendritic proteins halt and reverse...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29208644/filopodia-like-structure-formation-from-xenopus-egg-extracts
#9
Helen M Fox, Jennifer L Gallop
The actin cytoskeleton comprises many different architectures of filaments, including branched networks, parallel bundles and antiparallel fibers. A current challenge is to elucidate how the diverse array of actin regulators, which controls the growth, assembly and turnover of actin filaments, is used to orchestrate cytoskeletal organization and in turn cell shape and movement. Long observed to assemble at cell membranes, actin in Xenopus egg extracts recapitulates membrane-triggered assembly at specific lipid and membrane environments...
December 5, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29208529/vesicular-transport-protein-arf6-modulates-cytoskeleton-dynamics-for-polar-body-extrusion-in-mouse-oocyte-meiosis
#10
Xing Duan, Hao-Lin Zhang, Meng-Hao Pan, Yu Zhang, Shao-Chen Sun
Arf6 (ADP-ribosylation factor 6) is known to play important roles in membrane dynamics through the regulation of actin filament reorganization for multiple cellular processes such as cytokinesis, phagocytosis, cell migration and tumor cell invasion. However, the functions of Arf6 in mammalian oocyte meiosis have not been clarified. In present study we showed that Arf6 expressed in mouse oocytes and was mainly distributed around the spindle during meiosis. Depletion of Arf6 by morpholino microinjection caused oocytes failing to extrude first polar body...
December 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29190677/cortical-actin-nodes-their-dynamics-and-recruitment-of-podosomal-proteins-as-revealed-by-super-resolution-and-single-molecule-microscopy
#11
Yuki M Shirai, Taka A Tsunoyama, Nao Hiramoto-Yamaki, Koichiro M Hirosawa, Akihiro C E Shibata, Kenichi Kondo, Atsushi Tsurumune, Fumiyoshi Ishidate, Akihiro Kusumi, Takahiro K Fujiwara
Electron tomography of the plasma membrane (PM) identified several layers of cortical actin meshwork running parallel to the PM cytoplasmic surface throughout the PM. Here, cortical actin structures and dynamics were examined in living cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140 and ~400 nm, respectively, and single-molecule imaging. The super-resolution microscopy identified sub-micron-sized actin clusters that appeared identical by both phalloidin post-fixation staining and Lifeact-mGFP expression followed by fixation, and therefore, these actin clusters were named "actin-pl-clusters"...
2017: PloS One
https://www.readbyqxmd.com/read/29187576/host-cell-perforation-by-listeriolysin-o-llo-activates-a-ca2-dependent-cpkc-rac1-arp2-3-signaling-pathway-that-promotes-l-monocytogenes-internalization-independently-of-membrane-resealing
#12
Jonathan Lam, Stephen Vadia, Sarika Pathak-Sharma, Eric McLaughlin, Xiaoli Zhang, Joel Swanson, Stephanie Seveau
Host cell invasion is an indispensable step for a successful infection by intracellular pathogens. Recent studies identified pathogen-induced host cell plasma membrane perforation as a novel mechanism used by diverse pathogens (Trypanosoma cruzi, Listeria monocytogenes, and adenovirus) to promote their internalization into target cells. It was concluded that T. cruzi and adenovirus damage the host cell plasma membrane to hijack the endocytic-dependent membrane resealing machinery, thereby invading the host cell...
November 29, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29163156/role-of-translocator-18-kda-ligands-in-the-activation-of-leukotriene-b4-activated-g-protein-coupled-receptor-and-toll-like-receptor-4-pathways-in-neutrophils
#13
Léonard de Vinci Kanda Kupa, Carine C Drewes, Eric D Barioni, Camila L Neves, Sandra Coccuzzo Sampaio, Sandra H P Farsky
TSPO (Translocator 18 KDa; tryptophan-rich sensory protein oxygen sensor) is a constitutive outer mitochondrial membrane protein overexpressed in inflammatory cells during local or systemic processes. Despite its expression is characterized, role of TSPO in inflammation remains elusive. For this study, we investigated the role of TSPO ligands on neutrophil functions elicited by two different inflammatory pathways. Peritoneal neutrophils were isolated from male Balb-C mice, treated with TSPO ligand diazepam, Ro5-4864 or PK11195 (1,100 or 1000 nM; 2 h) and further stimulated with lipopolysaccharide from Escherichia coli (LPS), a binding for Toll-Like Receptor-4 (TLR4), or leukotriene B4 (LTB4), a G-protein coupled receptor (GPCR) ligand...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29162704/tropomyosin-related-kinase-c-trkc-enhances-podocyte-migration-by-erk-mediated-wave2-activation
#14
Sascha Gromnitza, Carolin Lepa, Thomas Weide, Albrecht Schwab, Hermann Pavenstädt, Britta George
Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). TrkC deficiency in mice leads to proteinuria as a surrogate of defective kidney filter function. Activation of endogenous TrkC by its ligand neurotrophin-3 resulted in increased podocyte migration-a surrogate of podocyte actin dynamics in vivo Employing a mutagenesis approach, we found that the Src homologous and collagen-like (Shc) binding site Tyr(516) within the TrkC cytoplasmic domain was necessary for TrkC-induced migration of podocytes...
November 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29162307/cortactin-cell-functions-of-a-multifaceted-actin-binding-protein
#15
REVIEW
Michael Schnoor, Theresia E Stradal, Klemens Rottner
Cortactin fulfills many functions in various cell types. These functions have been considered to derive from its ability to activate the Actin-related protein 2/3 (Arp2/3) complex, and are regulated by post-translational modifications, including phosphorylation and acetylation. New evidence suggests that cortactin regulates cell migration by controlling the deposition of extracellular matrix proteins rather than lamellipodial Arp2/3 activation, and that cortactin also functions in GTPase signaling, vesicular trafficking, and actomyosin contractility...
November 18, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/29152154/cortactin-in-cancer-cell-migration-and-invasion
#16
REVIEW
Miao Yin, Wenqing Ma, Liguo An
Cortactin, a substrate of sarcoma (Src) kinases, is an actin-binding protein that is involved in cytoskeletal regulation, and is frequently overexpressed in cancer cells. Binding to the actin related protein 2/3 (Arp2/3) complex stimulates cortactin activity, which promotes F-actin nucleation and assembly. Cortactin promotes cancer cell migration and invasion, and plays a pivotal role in invadopodia formation and extra cellular matrix degradation. Overexpression of cortactin, by amplification of the chromosomal band 11q13, increases tumor aggressiveness...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146997/a-new-method-to-measure-mechanics-and-dynamic-assembly-of-branched-actin-networks
#17
Pierre Bauër, Joseph Tavacoli, Thomas Pujol, Jessica Planade, Julien Heuvingh, Olivia du Roure
We measured mechanical properties and dynamic assembly of actin networks with a new method based on magnetic microscopic cylinders. Dense actin networks are grown from the cylinders' surfaces using the biochemical Arp2/3-machinery at play in the lamellipodium extension and other force-generating processes in the cell. Under a homogenous magnetic field the magnetic cylinders self-assemble into chains in which forces are attractive and depend on the intensity of the magnetic field. We show that these forces, from piconewtons to nanonewtons, are large enough to slow down the assembly of dense actin networks and controlled enough to access to their non linear mechanical responses...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141912/wh2-and-proline-rich-domains-of-wasp-family-proteins-collaborate-to-accelerate-actin-filament-elongation
#18
Peter Bieling, Scott D Hansen, Orkun Akin, Tai-De Li, Carl C Hayden, Daniel A Fletcher, R Dyche Mullins
WASP-family proteins are known to promote assembly of branched actin networks by stimulating the filament-nucleating activity of the Arp2/3 complex. Here, we show that WASP-family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP-family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline-rich sequence that binds profilin-actin complexes...
November 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29136780/cml-cd36-accelerates-atherosclerotic-progression-via-inhibiting-foam-cell-migration
#19
Suining Xu, Lihua Li, Jinchuan Yan, Fei Ye, Chen Shao, Zhen Sun, Zhengyang Bao, Zhiyin Dai, Jie Zhu, Lele Jing, Zhongqun Wang
Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29127144/disruption-of-thrombocyte-and-t-lymphocyte-development-by-a-mutation-in-arpc1b
#20
Raz Somech, Atar Lev, Yu Nee Lee, Amos J Simon, Ortal Barel, Ginette Schiby, Camila Avivi, Iris Barshack, Michele Rhodes, Jiejing Yin, Minshi Wang, Yibin Yang, Jennifer Rhodes, Nufar Marcus, Ben-Zion Garty, Jerry Stein, Ninette Amariglio, Gideon Rechavi, David L Wiest, Yong Zhang
Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott-Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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