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https://www.readbyqxmd.com/read/29152154/cortactin-in-cancer-cell-migration-and-invasion
#1
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
#2
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
#3
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
#4
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
#5
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...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29115292/fibronectin-bound-%C3%AE-5%C3%AE-1-integrins-sense-load-and-signal-to-reinforce-adhesion-in-less-than-a-second
#6
Nico Strohmeyer, Mitasha Bharadwaj, Mercedes Costell, Reinhard Fässler, Daniel J Müller
Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0...
November 6, 2017: Nature Materials
https://www.readbyqxmd.com/read/29113991/knockout-of-the-arp2-3-complex-in-epidermis-causes-a-psoriasis-like-disease-hallmarked-by-hyperactivation-of-transcription-factor-nrf2
#7
Rob van der Kammen, Ji-Ying Song, Iris de Rink, Hans Janssen, Stefania Madonna, Claudia Scarponi, Cristina Albanesi, Wim Brugman, Metello Innocenti
Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels...
November 7, 2017: Development
https://www.readbyqxmd.com/read/29104956/deletion-of-the-arp2-3-complex-in-megakaryocytes-leads-to-microthrombocytopenia-in-mice
#8
David S Paul, Caterina Casari, Congying Wu, Raymond Piatt, Swetha Pasala, Robert A Campbell, Kathryn O Poe, Dorsaf Ghalloussi, Robert H Lee, Jeremy D Rotty, Brian C Cooley, Kellie R Machlus, Joseph E Italiano, Andrew S Weyrich, James E Bear, Wolfgang Bergmeier
Actin reorganization regulates key processes in platelet activation. Here we examined the role of the Arp2/3 complex, an essential component in actin filament branching, in platelet function. The Arpc2 gene, encoding the p34 subunit of the Arp2/3 complex, was deleted in the megakaryocyte lineage (Arpc2(fl/fl)PF4-Cre). Deletion of the Arp2/3 complex resulted in marked microthrombocytopenia in mice, caused by premature platelet release into the bone marrow compartment and impaired platelet survival in circulation...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29100370/identification-of-the-pak4-interactome-reveals-pak4-phosphorylation-of-n-wasp-and-promotion-of-arp2-3-dependent-actin-polymerization
#9
Miao Zhao, Matthias Spiess, Henrik J Johansson, Helene Olofsson, Jianjiang Hu, Janne Lehtiö, Staffan Strömblad
p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed. Here, we comprehensively characterized the human PAK4 interactome by iTRAQ quantitative mass spectrometry of PAK4-immunoprecipitations. Consistent with its multiple reported functions, the PAK4 interactome was enriched in diverse protein networks, including the 14-3-3, proteasome, replication fork, CCT and Arp2/3 complexes. Because PAK4 co-immunoprecipitated most subunits of the Arp2/3 complex, we hypothesized that PAK4 may play a role in Arp2/3 dependent actin regulation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100335/breast-cancer-induced-nociceptor-aberrant-growth-and-collateral-sensory-axonal-branching
#10
Matt Austin, Laura Elliott, Niovi Nicolaou, Anna Grabowska, Richard P Hulse
The tumour and neuron interaction has a significant impact upon disease progression and the patients quality of life. In breast cancer patients, it is known that there is an interaction between the tumour microenvironment and the sensory neurons to influence the progression of cancer as well as pain, though these mechanisms still need to be clearly defined. Here it is demonstrated that in a rodent orthotopic model of breast cancer (MDA MB 231) there was an increase in nerve fibre innervation into the tumour microenvironment (protein gene product 9...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058690/advillin-acts-upstream-of-phospholipase-c-%C3%AF%C2%B51-in-steroid-resistant-nephrotic-syndrome
#11
Jia Rao, Shazia Ashraf, Weizhen Tan, Amelie T van der Ven, Heon Yung Gee, Daniela A Braun, Krisztina Fehér, Sudeep P George, Amin Esmaeilniakooshkghazi, Won-Il Choi, Tilman Jobst-Schwan, Ronen Schneider, Johanna Magdalena Schmidt, Eugen Widmeier, Jillian K Warejko, Tobias Hermle, David Schapiro, Svjetlana Lovric, Shirlee Shril, Ankana Daga, Ahmet Nayir, Mohan Shenoy, Yincent Tse, Martin Bald, Udo Helmchen, Sevgi Mir, Afig Berdeli, Jameela A Kari, Sherif El Desoky, Neveen A Soliman, Arvind Bagga, Shrikant Mane, Mohamad A Jairajpuri, Richard P Lifton, Seema Khurana, Jose C Martins, Friedhelm Hildebrandt
Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex...
October 23, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29057977/myosin-x-is-recruited-to-nascent-focal-adhesions-at-the-leading-edge-and-induces-multi-cycle-filopodial-elongation
#12
Kangmin He, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Tomonobu M Watanabe, Mitsuo Ikebe
Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053324/variability-and-order-in-cytoskeletal-dynamics-of-motile-amoeboid-cells
#13
Hsin-Fang Hsu, Eberhard Bodenschatz, Christian Westendorf, Azam Gholami, Alain Pumir, Marco Tarantola, Carsten Beta
The chemotactic motion of eukaryotic cells such as leukocytes or metastatic cancer cells relies on membrane protrusions driven by the polymerization and depolymerization of actin. Here we show that the response of the actin system to a receptor stimulus is subject to a threshold value that varies strongly from cell to cell. Above the threshold, we observe pronounced cell-to-cell variability in the response amplitude. The polymerization time, however, is almost constant over the entire range of response amplitudes, while the depolymerization time increases with increasing amplitude...
October 6, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29049733/tunneling-nanotubes-are-novel-cellular-structures-that-communicate-signals-between-trabecular-meshwork-cells
#14
Kate E Keller, John M Bradley, Ying Ying Sun, Yong-Feng Yang, Ted S Acott
Purpose: The actin cytoskeleton of trabecular meshwork (TM) cells plays a role in regulating aqueous humor outflow. Many studies have investigated stress fibers, but F-actin also assembles into other supramolecular structures including filopodia. Recently, specialized filopodia called tunneling nanotubes (TNTs) have been described, which communicate molecular signals and organelles directly between cells. Here, we investigate TNT formation by TM cells. Methods: Human TM cells were labeled separately with the fluorescent dyes, DiO and DiD, or with mitochondrial dye...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28983581/bioinformatics-analysis-of-fibroblasts-exposed-to-tgf%C3%A2-%C3%AE-at-the-early-proliferation-phase-of-wound-repair
#15
Bobin Mi, Guohui Liu, Wu Zhou, Huijuan Lv, Kun Zha, Yi Liu, Qipeng Wu, Jing Liu
The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF‑β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co‑expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28972183/the-actin-related-p41arc-subunit-contributes-to-p21-activated-kinase-1-pak1-mediated-glucose-uptake-into-skeletal-muscle-cells
#16
Ragadeepthi Tunduguru, Jing Zhang, Arianne Aslamy, Vishal A Salunkhe, Joseph T Brozinick, Jeffrey S Elmendorf, Debbie C Thurmond
Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, pre-clinical diabetes, and progression to type 2 diabetes. GLUT4 recruitment to the plasma membrane of skeletal muscle cells requires filamentous (F)-actin remodeling. Insulin signaling in muscle requires p21-activated kinase-1 (PAK1), whose downstream signaling triggers actin remodeling that promotes GLUT4 vesicle translocation and glucose uptake into skeletal muscle cells. Actin remodeling is a cyclic process, and while PAK1 is known to initiate changes to the cortical actin-binding protein cofilin to stimulate the depolymerizing arm of the cycle, how PAK1 might trigger the polymerizing arm of the cycle remains unresolved...
September 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28949297/rac1-gtpase-activates-the-wave-regulatory-complex-through-two-distinct-binding-sites
#17
Baoyu Chen, Hui-Ting Chou, Chad A Brautigam, Wenmin Xing, Sheng Yang, Lisa Henry, Lynda K Doolittle, Thomas Walz, Michael K Rosen
The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation...
September 26, 2017: ELife
https://www.readbyqxmd.com/read/28948912/actin-based-protrusions-of-migrating-neutrophils-are-intrinsically-lamellar-and-facilitate-direction-changes
#18
Lillian K Fritz-Laylin, Megan Riel-Mehan, Bi-Chang Chen, Samuel J Lord, Thomas D Goddard, Thomas E Ferrin, Susan M Nicholson-Dykstra, Henry Higgs, Graham T Johnson, Eric Betzig, R Dyche Mullins
Leukocytes and other amoeboid cells change shape as they move, forming highly dynamic, actin-filled pseudopods. Although we understand much about the architecture and dynamics of thin lamellipodia made by slow-moving cells on flat surfaces, conventional light microscopy lacks the spatial and temporal resolution required to track complex pseudopods of cells moving in three dimensions. We therefore employed lattice light sheet microscopy to perform three-dimensional, time-lapse imaging of neutrophil-like HL-60 cells crawling through collagen matrices...
September 26, 2017: ELife
https://www.readbyqxmd.com/read/28938568/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#19
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938008/vca-nanobodies-target-n-wasp-to-reduce-invadopodium-formation-and-functioning
#20
Tim Hebbrecht, Isabel Van Audenhove, Olivier Zwaenepoel, Adriaan Verhelle, Jan Gettemans
Invasive cancer cells develop small actin-based protrusions called invadopodia, which perform a primordial role in metastasis and extracellular matrix remodelling. Neural Wiskott-Aldrich syndrome protein (N-WASp) is a scaffold protein which can directly bind to actin monomers and Arp2/3 and is a crucial player in the formation of an invadopodium precursor. Expression modulation has pointed to an important role for N-WASp in invadopodium formation but the role of its C-terminal VCA domain in this process remains unknown...
2017: PloS One
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