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| Open AccessDynamic actin cycling through mitochondrial subpopulations locally regulates the fission–fusion balance within mitochondrial networks
Mitochondria are dynamic organelles that can undergo fission and fusion. Here the authors identify a novel pathway in which actin dynamically assembles in an Arp2/3- and formin-dependent manner around a subset of cellular mitochondria, promoting localized Drp1-dependent fission and impeding fusion.
- Andrew S. Moore
- , Yvette C. Wong
- & Erika L. F. Holzbaur
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Article
| Open AccessActin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane
As vesicles fuse to the plasma membrane, they form intermediate Ω-shaped structures followed by either closure of the pore or full merging with the plasma membrane. Here Wen et al. show that dynamic actin assembly provides membrane tension to promote Ω merging in neuroendocrine cells and synapses.
- Peter J. Wen
- , Staffan Grenklo
- & Ling-Gang Wu
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Article
| Open AccessDisordered actomyosin networks are sufficient to produce cooperative and telescopic contractility
The interaction between myosin motors and F-actin is well described, but the impact of actin organization on contractility is not well described. Here the authors use a 2D biomimetic system and computational modelling to show that contractility of isotropic actomyosin is cooperative, and contraction velocity scales with myosin activation area.
- Ian Linsmeier
- , Shiladitya Banerjee
- & Michael P. Murrell
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| Open AccessFscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation
It is unclear how the cytoskeleton acts to assist in TGF-β signalling downstream of the receptor. Here, in zebrafish, the authors show that the actin-bundling protein FSCN1 interacts with TGF-β type I receptors ALK 4 and 5, enabling actin filament mediated vesicle trafficking and endoderm formation.
- Zhaoting Liu
- , Guozhu Ning
- & Qiang Wang
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| Open AccessIdentification of an ATP-controlled allosteric switch that controls actin filament nucleation by Arp2/3 complex
Arp2/3 complex nucleates branched actin filaments, and is inactive in the absense of activators. Here the authors present a model of Arp2/3 autoinhibition, whereby the Arp3 C-terminal tail acts as a structural switch that blocks movement of Arp2 and Arp3 into an activated filament-like conformation.
- Max Rodnick-Smith
- , Su-Ling Liu
- & Brad J. Nolen
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Article
| Open AccessFimbrin phosphorylation by metaphase Cdk1 regulates actin cable dynamics in budding yeast
Metaphase cells preferentially promote actin cable assembly through cyclin-dependent kinase 1 (Cdk1) activity. Here the authors identify fimbrin as one of the main metaphase Cdk1 targets for cell cycle regulation of actin cable assembly in budding yeast.
- Yansong Miao
- , Xuemei Han
- & David G. Drubin
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Article
| Open AccessActin nucleation at the centrosome controls lymphocyte polarity
Cell polarity is marked by re-orientation of the centrosome, but the mechanisms governing centrosome polarization are poorly understood. Here Obino et al. show that in lymphocytes centrosome-associated Arp2/3 nucleates actin that tethers the centrosome to the nucleus; activation depletes Arp2/3 from the centrosome and frees it from the nucleus.
- Dorian Obino
- , Francesca Farina
- & Ana-Maria Lennon-Duménil
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| Open AccessPerinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments
Cell migration through micrometric constraints is limited by low deformability of the nucleus. Here the authors show that in dendritic cells a perinuclear actin network nucleated by Arp2/3 increases nuclear deformation and allows the cells to pass through narrow constrictions, likely by rupturing the nuclear lamina.
- Hawa-Racine Thiam
- , Pablo Vargas
- & Matthieu Piel
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Article
| Open AccessF-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling
Endothelial cells can support leukocyte extravasation without causing vascular leakage, but the exact mechanism underlying this process has not been fully elucidated. Here the authors show that it is regulated through actomyosin-based endothelial pore confinement, which requires local endothelial RhoA activation.
- Niels Heemskerk
- , Lilian Schimmel
- & Jaap D. van Buul
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Article
| Open AccessF-actin mechanics control spindle centring in the mouse zygote
How the mitotic spindle is positioned in the centre of the cell during the first mitotic division is not clear. Here Chaigne et al.show that the pronucleus coarsely centres using F-actin/Myosin-Vb dynamics, and the metaphase plate is finely centred by an F-actin cage influenced by high cortical tension.
- Agathe Chaigne
- , Clément Campillo
- & Marie-Emilie Terret
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Article
| Open AccessArp2/3-mediated F-actin formation controls regulated exocytosis in vivo
The cytoskeleton plays a crucial role in secretion. Here Tran et al.demonstrate that cortical actin is rearranged at the site of vesicle fusion and recruited to fused secretory granules in Drosophila salivary glands, and show that branched actin nucleators are required for cargo expulsion.
- Duy T. Tran
- , Andrius Masedunskas
- & Kelly G. Ten Hagen
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Article
| Open AccessA molecular ruler regulates cytoskeletal remodelling by the Rho kinases
Rho kinases regulate the actin cytoskeleton by controlling stress fibre formation. Truebestein et al.show that the length of its coiled-coil determines ROCK2 function, and propose that the coiled coil acts as a spacer, targeting kinase activity to a discrete distance from the membrane.
- Linda Truebestein
- , Daniel J. Elsner
- & Thomas A. Leonard
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Article
| Open AccessMitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement
In epithelial layers cells must round up prior to division. Here the authors use micropillar arrays to mimic epithelial confinement and show that MDCK cells generate force to create space to divide; if unable to generate sufficient force they escape the micropillars to divide and return to confinement.
- Barbara Sorce
- , Carlos Escobedo
- & Daniel J. Müller
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| Open AccessSingle-molecule visualization of a formin-capping protein ‘decision complex’ at the actin filament barbed end
Formins promote the polymerization of actin filaments at barbed ends and capping protein prevents polymerization. Here the authors use single molecule imaging to directly visualize a decision complex consisting of the formin mDia1 and capping protein bound simultaneously to the filament barbed end and the dynamic mechanisms by which it forms and dissociates.
- Jeffrey P. Bombardier
- , Julian A. Eskin
- & Jeff Gelles
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| Open AccessFormin and capping protein together embrace the actin filament in a ménage à trois
Formins promote actin filament polymerization and capping protein blocks polymerization; both proteins are thought to exclude each other from barbed ends. Here the authors show that both proteins can simultaneously bind barbed ends in a ternary complex while enhancing each other's dissociation from the barbed end.
- Shashank Shekhar
- , Mikael Kerleau
- & Marie-France Carlier
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| Open AccessPhosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins
Phagocytosis of large (but not small) particles requires PI 3-kinase activity. Here, Schlam et al. show that Rho GTPase-activating proteins are recruited to the phagocytic cup by products of PI 3-kinase, resulting in the local inactivation of Rac and Cdc42 and allowing for the completion of internalization of large particles.
- Daniel Schlam
- , Richard D. Bagshaw
- & Sergio Grinstein
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Article
| Open AccessA RIAM/lamellipodin–talin–integrin complex forms the tip of sticky fingers that guide cell migration
The leading edge of migrating cells contains activated integrins associated with growing actin filaments that form ‘sticky fingers’ to guide cell migration. Here, the authors detect a complex of MRL proteins, talin and activated integrins in lamellipodia and filopodia in living cells, comprising the tips of the ‘sticky fingers’.
- Frederic Lagarrigue
- , Praju Vikas Anekal
- & Mark H. Ginsberg
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| Open AccessA resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement
Amoeboid motility is driven by actomyosin-based contraction and exploits differences in the mechanical properties of the cortical cytoskeleton. Here the authors discover that mDia1-like formin A is responsible for generating a subset of actin filaments at the rear of Dictyosteliumthat suppresses lateral protrusions and blebbing during 2D-confined migration.
- Nagendran Ramalingam
- , Christof Franke
- & Jan Faix
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Article
| Open AccessCPI motif interaction is necessary for capping protein function in cells
Capping protein regulates actin filament dynamics by binding to barbed ends and preventing their growth. Edwards et al. show that capping protein also requires interactions with proteins containing a capping protein interaction motif to promote its proper localization and regulation of actin dynamics.
- Marc Edwards
- , Patrick McConnell
- & John A. Cooper
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Article
| Open AccessmiR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
MicroRNAs of the miR-34/449 family initiate formation of multiciliated cells through the suppression of cell cycle genes and Notch. Here the authors show that miR-34/449 also regulate the assembly of an apical actin network necessary for basal body anchoring by regulating the expression of R-Ras.
- Benoît Chevalier
- , Anna Adamiok
- & Brice Marcet
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| Open AccessHow Leiomodin and Tropomodulin use a common fold for different actin assembly functions
Leiomodins and Tropomodulins are related, but have different functions; actin filament nucleation and pointed end capping, respectively. Here, the authors use structural, biochemical and cellular approaches to show how these different activities have evolved based on a common protein fold.
- Malgorzata Boczkowska
- , Grzegorz Rebowski
- & Roberto Dominguez
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Article
| Open AccessActin nucleation by WH2 domains at the autophagosome
Autophagy is a catabolic process whereby cellular components are degraded by the autophagosome, but the role of the actin cytoskeleton is not clear. Here Coutts and La Thangue show that the actin nucleator JMY is recruited to the autophagosome via binding LC3, and promotes actin nucleation that is required for autophagosome maturation.
- Amanda S. Coutts
- & Nicholas B. La Thangue
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| Open AccessAn actin-dependent spindle position checkpoint ensures the asymmetric division in mouse oocytes
In mammalian oocytes, the meiotic spindle is assembled close to the centre of the cell and relocates to the cell periphery prior to chromosome segregation. Here Metchat et al. show that anaphase is delayed until the spindle is positioned close to the cell cortex, providing evidence for a spindle position checkpoint.
- Aïcha Metchat
- , Manuel Eguren
- & Jan Ellenberg
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Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction
Muscle function depends on a highly organized array of actin and myosin filaments. Butkevichet al. identify the C. elegansdrebrin-like protein DBN-1 as an important regulator of actin filament stability in muscle cells, which relocalises from M-lines to I-bands on contraction.
- Eugenia Butkevich
- , Kai Bodensiek
- & Dieter R. Klopfenstein
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Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing
Adherent cells actively probe the rigidity of their substrates. Guptaet al. show that actin cytoskeleton rheology transitions from fluid to solid with increased substrate stiffness along with an isotropic to nematic ordering, implicating the remodelling of the whole actin network in rigidity sensing.
- Mukund Gupta
- , Bibhu Ranjan Sarangi
- & Benoît Ladoux
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Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization
As metastasis requires cellular machinery of migration and invasion, interfering with these functions is a promising anticancer strategy. Here the authors show that a structurally novel fascin inhibitor blocks filopodia formation, migration and invasion, and effectively inhibits metastasis in mice.
- Fang-Ke Huang
- , Shaoqin Han
- & Xin-Yun Huang
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Article
| Open AccessPlatelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
During early platelet spreading a novel F-actin structure forms, called the actin nodule. Here Poulter et al.demonstrate that actin nodule formation depends on WASp and the Arp2/3 complex, and using super-resolution microscopy they show that nodules bear a structural resemblance to podosomes.
- Natalie S. Poulter
- , Alice Y. Pollitt
- & Steven G. Thomas
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| Open AccessCapping protein integrates multiple MAMP signalling pathways to modulate actin dynamics during plant innate immunity
Cytoskeletal remodelling is an important component of the innate immune response in plants. Here, Li et al. demonstrate that pathogen-triggered actin remodelling is due to the inhibition of capping protein (CP), and show that CP is required for resistance against plant pathogens.
- Jiejie Li
- , Jessica L. Henty-Ridilla
- & Christopher J. Staiger
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| Open AccessSingle-molecule imaging of a three-component ordered actin disassembly mechanism
The roles of Coronin, Cofilin and AIP1 in promoting actin disassembly have not been well understood. Here using single-molecule fluorescence imaging, Jansen et al. show that the three proteins act together in a coordinated, temporal pathway to induce rapid severing and disassembly of actin filaments.
- Silvia Jansen
- , Agnieszka Collins
- & Bruce L. Goode
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| Open AccessThe structure of FMNL2–Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation
FMNL formins polymerize actin filaments to generate cellular protrusions such as lamellipodia and filopodia at the leading edge of a cell. Here the authors provide detailed mechanistic insights into the formation of actin-based protrusions through GTPase dependent activation and membrane localization of FMNL1 and FMNL2.
- Sonja Kühn
- , Constanze Erdmann
- & Matthias Geyer
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| Open AccessLive-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear
Precise control of stereocilia length by auditory hair cells is vital for normal hearing. Drummond et al. follow in real-time the incorporation of actin into these structures and show that while the actin core is remarkably stable, and actin polymerization is limited to their distal tips.
- Meghan C. Drummond
- , Melanie Barzik
- & Thomas B. Friedman
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Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking
Destabilizing the actin cytoskeleton induces the formation of primary cilia, but the mechanism is unknown. Here, Kim et al.show that activity of the transcriptional coactivators YAP/TAZ is regulated by actin remodelling factors, and YAP/TAZ activity correlates with ciliogenesis.
- Jongshin Kim
- , Haiin Jo
- & Joon Kim
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| Open AccessToll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor
Microbial pathogens can activate both innate and adaptive receptors, and integration of these signals may enhance the sensitivity of the immune response. Freeman et al. show that innate microbial cues sensitize B cells to antigen by increasing actin dynamics and reducing the actin-dependent confinement of the B-cell receptor.
- Spencer A. Freeman
- , Valentin Jaumouillé
- & Michael R. Gold
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| Open AccessTropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling
Insulin-stimulated GLUT4-storage vesicle fusion with the plasma membrane depends on activity of Akt2 and its downstream effectors. Here Lim et al.identify the actin-capping protein tropomodulin 3 as a novel Akt2 effector that remodels cortical actin to help facilitate GLUT4 membrane insertion.
- Chun-Yan Lim
- , Xuezhi Bi
- & Weiping Han
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Epithelial rotation promotes the global alignment of contractile actin bundles during Drosophila egg chamber elongation
During Drosophilaoogenesis, migration of follicle cells causes the egg chamber to rotate, changing the shape of the egg chamber from spherical to oval. Here the authors show, using live imaging, that lamellopodia on the follicle cells are required for this rotation and alignment of contractile actin bundles.
- Maureen Cetera
- , Guillermina R. Ramirez-San Juan
- & Sally Horne-Badovinac
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The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics
The mammalian subcortical maternal complex is composed of maternally expressed proteins and required for mouse early embryonic cell division. Here the authors show that the complex functions to control spindle positioning through regulation of the actin cytoskeleton.
- Xing-Jiang Yu
- , Zhaohong Yi
- & Lei Li
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Article
| Open AccessActin–microtubule coordination at growing microtubule ends
The structural cross-talk between components of the eukaryotic cytoskeleton remains poorly understood. Here the authors engineer an actin-binding microtubule tip-tracking protein that guides microtubule growth along actin bundles, and allows microtubule growing ends to pull and bundle actin filaments.
- Magdalena Preciado López
- , Florian Huber
- & Marileen Dogterom
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Documentation and localization of force-mediated filamin A domain perturbations in moving cells
Biosensors designed to respond to mechanical force in cells have provided insights into the force landscape within a cell. Here, Nakamura et al. design a FRET probe in the actin crosslinking protein filamin A and show that it unfolds under force only in newly protruding regions of the cell.
- Fumihiko Nakamura
- , Mia Song
- & Thomas P. Stossel
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AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion
Cell–cell adhesion molecules and the cytoskeleton determine endothelial cell shape during the formation of blood vessels. Here the authors show that the scaffold protein, amotL2, couples adherens junctions to contractile cytoskeletal proteins to coordinate cellular morphogenesis with aortic lumen expansion.
- Sara Hultin
- , Yujuan Zheng
- & Lars Holmgren
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Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation
Adipocyte differentiation is accompanied by large scale changes in the actin cytoskeleton. Here, Nobusue et al.show that binding to G-actin sequesters the transcriptional coactivator MKL1 in the cytoplasm, and triggers differentiation by inducing the expression of pro-adipogenic transcription factor PPARγ.
- Hiroyuki Nobusue
- , Nobuyuki Onishi
- & Koichiro Kano
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Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs
The involvement of one or two nucleation-promoting factors in Arp2/3 complex activation is a matter of debate. Here Boczkowska et al.provide evidence that two nucleation-promoting factors are required, and propose a model of the 11-subunit transitional complex based on distance measurements by FRET.
- Malgorzata Boczkowska
- , Grzegorz Rebowski
- & Roberto Dominguez
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Article
| Open AccessActomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring
The interaction between focal adhesion proteins vinculin and talin is stimulated by mechanical stretching. Here the authors reconstitute actomyosin-dependent stretching of talin in vitro, and show that the resulting activation of vinculin reinforces anchoring of the adhesion complex to actin.
- Corina Ciobanasu
- , Bruno Faivre
- & Christophe Le Clainche
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| Open AccessGuidance of subcellular tubulogenesis by actin under the control of a synaptotagmin-like protein and Moesin
The terminal branches of the Drosophilatracheal network have intracellular tubules that grow through elongation of membrane invaginations. Here, the authors identify the synaptotagmin-like protein Bitesize as a regulator of actin-dependent luminal membrane morphogenesis.
- N. JayaNandanan
- , Renjith Mathew
- & Maria Leptin
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Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics
Nck1/2 adaptor proteins control the assembly and activity of protein complexes that promote actin polymerization. Buvall et al.show that Nck1 abundance is regulated by the E3 ubiquitin ligase c-Cbl, which competes for Nck binding with the actin-binding protein synaptopodin in podocytes.
- Lisa Buvall
- , Priyanka Rashmi
- & Peter Mundel
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The unusual dynamics of parasite actin result from isodesmic polymerization
Actin normally polymerizes into filaments in a cooperative manner, with nucleation and elongation phases. Skillman et al. show that actin from the protozoan parasite Toxoplasma gondiipolymerizes in an isodesmic manner, without any evidence of nucleation, resulting in filaments that are very short and unstable.
- Kristen M. Skillman
- , Christopher I. Ma
- & L. David Sibley
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Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics
While small molecules that destabilize actin filaments are readily available, artificially stimulating actin polymerization in cells typically involves genetic manipulation. Here, the authors design cell-permeable branched polyamines that promote lamellipodium formation by stimulating actin polymerization.
- Iliana Nedeva
- , Girish Koripelly
- & Daniel Riveline
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Formin mDia1 senses and generates mechanical forces on actin filaments
Formins are a family of protein complexes that accelerate actin filament nucleation and elongation. Jegou et al.show that the formin mDia1 can generate mechanical tension in actin filaments, while conversely, pulling forces applied by viscous drag increase formin elongation activity.
- Antoine Jégou
- , Marie-France Carlier
- & Guillaume Romet-Lemonne
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Article
| Open AccessInterplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations
Dendritic cells use protrusive structures called podosomes to probe the extracellular environment. Here the authors reveal how interplay between actin-mediated core growth and myosin-mediated tension regulates podosome protrusion.
- K. van den Dries
- , M.B.M Meddens
- & A. Cambi
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Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks
Processes that regulate the mechanical and dynamic properties of actin cytoskeleton are important for multiple eukaryotic cell functions. In this study, using reconstituted crosslinked actin networks, organization is found to be determined by the competing kinetics of actin gelation and bundle formation.
- Tobias T. Falzone
- , Martin Lenz
- & Margaret L. Gardel