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| Open AccessFocal adhesions contain three specialized actin nanoscale layers
Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.
- Reena Kumari
- , Katharina Ven
- & Pekka Lappalainen
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Article
| Open AccessCytokinetic abscission requires actin-dependent microtubule severing
Completion of cell division requires severing both the microtubules and the plasma membrane that connects daughter cells. Here, the authors show that branched actin regulates ESCRT localization to promote the microtubule cut, which happens before membrane scission.
- Tamara Advedissian
- , Stéphane Frémont
- & Arnaud Echard
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Article
| Open AccessJAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development
The authors identified a cell population in Drosophila follicles that elaborate filopodia penetrating the oocyte they are contacting. These somatic cells are essential during oogenesis to regulate polarity and germline development of the future embryo.
- Charlotte Mallart
- , Sophie Netter
- & Marianne Malartre
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Article
| Open AccessIdentification of structural and regulatory cell-shape determinants in Haloferax volcanii
Key cellular processes, such as cell-shape determination, are poorly understood in archaea. Here, Schiller et al. study the model archaeon Haloferax volcanii, which forms rods and disks, and identify a diverse set of proteins important for these processes, including a new actin homolog that plays a role in the formation of disk-shaped cells.
- Heather Schiller
- , Yirui Hong
- & Mechthild Pohlschroder
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Article
| Open AccessHKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression
Aberrant expression of the human hexokinase HKDC1 has been observed in patients with cancer. Here the authors report that HKDC1 expression is associated with hepatocellular carcinoma progression and PD-L1 mediated immune evasion.
- Yi Zhang
- , Mingjie Wang
- & Ping Gao
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Article
| Open AccessIn situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Here, authors report the in situ structure of actin remodeling and quantify changes in architecture, alignment, and interactions during glucose-stimulated insulin secretion.
- Weimin Li
- , Angdi Li
- & Liping Sun
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Article
| Open AccessEmergence of periodic circumferential actin cables from the anisotropic fusion of actin nanoclusters during tubulogenesis
Periodic circumferential cytoskeletons support biological tube formation. Here, the authors show that self-assembled actin nanoclusters undergo biased fusion and develop into periodic cables in response to the membrane anisotropy of the expanding Drosophila tracheal tube.
- Sayaka Sekine
- , Mitsusuke Tarama
- & Shigeo Hayashi
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Article
| Open AccessOligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension
The cell biological mechanisms that govern myelin sheath extension remain incompletely understood. Here, the authors find that calcium signaling in oligodendrocytes is required for the actin-dependent extension of myelin sheaths.
- Manasi Iyer
- , Husniye Kantarci
- & J. Bradley Zuchero
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Article
| Open AccessForce transmission by retrograde actin flow-induced dynamic molecular stretching of Talin
Focal adhesion proteins transmit intracellular forces to the extracellular matrix (ECM). Here, the authors show a force transmission by elastic transient clutch of Talin between ECM and constantly flowing F-actin at focal adhesions.
- Sawako Yamashiro
- , David M. Rutkowski
- & Naoki Watanabe
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Article
| Open AccessRho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles
Cell movements are achieved by the spatio-temporal coordination of local membrane protrusions and retractions. Here, the authors identify a mechanism by which these protrusion and retraction events are coupled and how this affects the directionality of cell movements.
- Suchet Nanda
- , Abram Calderon
- & Leif Dehmelt
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Article
| Open AccessGRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis
Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.
- Qiang Zhu
- , Matthew E. Combs
- & Joan M. Taylor
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Article
| Open AccessIntracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Biosensors so far have mostly reported external traction forces exerted against the extracellular matrix or within adhesion receptors. Here, the authors present a sensor that reports molecular tension within the F-actin cytoskeleton.
- Sorosh Amiri
- , Camelia Muresan
- & Michael Murrell
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Article
| Open AccessCytosolic actin isoforms form networks with different rheological properties that indicate specific biological function
β-actin and γ-actin are nearly identical, and yet incorporate into different cytoskeletal structures. Here, the authors create isoform-pure reconstituted networks and study their structural and mechanical differences, underscoring the significance of the isoforms in diverse cellular functions.
- Peter Nietmann
- , Kevin Kaub
- & Andreas Janshoff
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Article
| Open AccessHIV-1 diverts cortical actin for particle assembly and release
HIV-1 assembles and buds from the host cell membrane of infected T lymphocytes. Here, Dibsy et al. characterise the role of cortical actin, viral Gag and host factor Arpin in virion assembly and release.
- Rayane Dibsy
- , Erwan Bremaud
- & Delphine Muriaux
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Article
| Open AccessMechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins
Arp2/3 complex is activated by nucleation promoting factors (NPFs) to form actin branches that are stabilized by cortactin. Here, the authors show that NPFs and cortactin activate Arp2/3 complex synergistically by helping recruit the complex to F-actin and by stabilizing its active conformation
- Fred E. Fregoso
- , Malgorzata Boczkowska
- & Roberto Dominguez
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Article
| Open AccessMYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM)
Arrhythmogenic cardiomyopathy is an untreatable heart muscle disease and a common cause of sudden cardiac death in young athletes. The authors show a link between actomyosin dysregulation and cardiac dysfunction by studying nonsense PKP2 mutants classified as pathogenic to identify a potential treatment.
- Nieves García-Quintáns
- , Silvia Sacristán
- & Juan A. Bernal
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Article
| Open AccessNET4 and RabG3 link actin to the tonoplast and facilitate cytoskeletal remodelling during stomatal immunity
Protein tethers can bridge the actin cytoskeleton with cellular membranes. Here, the authors show that two members of the NETWORKED family, NET4A and NET4B, tether actin filaments and the tonoplast through interaction with RABG3b and are essential for actin reorganization during stomatal closure in plant immunity.
- Timothy J. Hawkins
- , Michaela Kopischke
- & Silke Robatzek
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Article
| Open AccessN-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization
SUMOylation plays a key role in modulating protein function. Here, the authors uncover a form of SUMOylation, termed N-αSUMOylation, where SUMO1 attaches to the N-terminus of cofilin1. This SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization.
- Weiji Weng
- , Xiaokun Gu
- & Yong Li
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Article
| Open AccessEndothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels
Endothelial cell CD36 controls tissue fatty acid uptake. Here the authors show how fatty acid uptake by endothelial cells involves regulation of membrane ceramide production, caveolae dynamics, and exosome generation, these events facilitate transfer of circulating fatty acids to tissues and communication between endothelium and parenchyma.
- V. S. Peche
- , T. A. Pietka
- & N. A. Abumrad
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Article
| Open AccessMulticomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein
Actin networks in eukaryotic cells mediate essential processes such as cell migration, endocytosis, and morphogenesis. Here, using microfluidics assisted TIRF microscopy, the authors investigate how actin barbed-end polymerases, cappers, and depolymerases cooperate to regulate assembly of these networks.
- Heidi Ulrichs
- , Ignas Gaska
- & Shashank Shekhar
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Article
| Open AccessNuclear myosin VI maintains replication fork stability
Whether actin and associated molecules have roles in the nucleus is an active area of study. Here Shi et al. report a nuclear function of the actin-based motor myosin VI in protecting stalled replication forks from nuclease-mediated degradation.
- Jie Shi
- , Kristine Hauschulte
- & Hans-Peter Wollscheid
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Article
| Open AccessPPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex
The WAVE regulatory complex activates Arp2/3 at the cell cortex and in membrane protrusions to generate persistent cell migration. Here authors show that PPP2R1A, a scaffold subunit of protein phosphatase 2, associates with an alternative form of the WAVE complex where WAVE, the subunit that activates Arp2/3, is replaced by NHSL1.
- Yanan Wang
- , Giovanni Chiappetta
- & Alexis M. Gautreau
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Article
| Open AccessTwo RhoGEF isoforms with distinct localisation control furrow position during asymmetric cell division
This study provides evidence that two RhoGEF isoforms displaying distinct localisation concurrently modulate Rho1 activity to promote robust furrow ingression while preserving cell size asymmetry during neural stem cell division.
- Emilie Montembault
- , Irène Deduyer
- & Anne Royou
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Article
| Open AccessQuantitative structured illumination microscopy via a physical model-based background filtering algorithm reveals actin dynamics
Quantitative live-cell superresolution imaging that maintains the linearity of fluorescence signals remains difficult. Here, the authors propose a physical model-based background filtering method for 2D-SIM, which allows for quantitative imaging and high signal completeness.
- Yanquan Mo
- , Kunhao Wang
- & Liangyi Chen
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Article
| Open AccessA Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly
YAP signaling has been established as a mechanotransductive pathway in multiple contexts, but its developmental roles are still being explored. Here they show that YAP signaling sustains intracellular tension to direct cell migration during embryonic axis assembly.
- Ana Sousa-Ortega
- , Javier Vázquez-Marín
- & Juan R. Martínez-Morales
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Article
| Open AccessAn actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis
The authors find that the ciliopathy-associated protein Oral-Facial-Digital syndrome 1 functions as a class II nucleation promoting factor to drive actin filament branching, required for cell cycle progression. Interferring with this function suppresses cancer cell growth.
- Muqing Cao
- , Xiaoxiao Zou
- & Qing Zhong
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Article
| Open AccessAntigen discrimination by T cells relies on size-constrained microvillar contact
T cells can use TCR on microvilli to interact with peptide-MHC (pMHC) complexes on antigen presenting cells. Here the authors characterise how T cells use microvilli to interrogate reconstituted membranes for pMHC complexes and how this is regulated by a balance between glycoproteins/glycocalyces that reduce detection, and the small adhesion protein CD2, which enhances detection.
- Edward Jenkins
- , Markus Körbel
- & David Klenerman
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Article
| Open AccessCellular mechanisms of heterogeneity in NF2-mutant schwannoma
Schwannomas are mainly caused by NF2 tumour suppressor inactivation, but they display intratumoural heterogeneity. Here the authors show that this heterogeneity is caused by the loss of polarity and acquisition of different programmes of ErbB ligand production in NF2-mutant Schwann cells.
- Christine Chiasson-MacKenzie
- , Jeremie Vitte
- & Andrea I. McClatchey
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Article
| Open AccessTyrosyl-tRNA synthetase has a noncanonical function in actin bundling
Mutations in tRNA ligases, essential components of the translational machinery, are associated with Charcot-Marie-Tooth peripheral neuropathy, but the mechanistic details are not known. The authors report that the tyrosyl-tRNA synthetase is an evolutionary-conserved F-actin organizer, and dysregulation of this function is associated with the disorder.
- Biljana Ermanoska
- , Bob Asselbergh
- & Albena Jordanova
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Article
| Open AccessActin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives
In this work, the authors identify regulators of actin filament assembly involved in chiral organisation of the actin cytoskeleton in single cells and chiral alignment of cells in groups. This provides insights into how actin-driven chirality underlies tissue and organ asymmetry.
- Yee Han Tee
- , Wei Jia Goh
- & Alexander D. Bershadsky
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Article
| Open AccessTRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity
The cortical actin cytoskeleton plays a role in maintaining intestinal epithelial integrity. Here the authors report that TRIM40, an E3 ligase, disrupts cortical actin formation and leads to loss of epithelial barrier integrity, and that genetic loss of TRIM40 is protective against experimental colitis in male mice.
- Sujin Kang
- , Jaekyung Kim
- & Boyoun Park
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Article
| Open AccessHomeotic compartment curvature and tension control spatiotemporal folding dynamics
Morphogenetic shape changes are regulated by mechanical properties of interacting tissues, but other factors remain less studied. By exploring how homeotic genes regulate morphogenesis, Villedieu et al. uncover how the interplay between genetic patterning and initial tissue geometry drives morphogenesis during development.
- Aurélien Villedieu
- , Lale Alpar
- & Yohanns Bellaïche
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Article
| Open AccessWnt4 and ephrinB2 instruct apical constriction via Dishevelled and non-canonical signaling
Apical constriction is known to be critical for neural tube closure, but the signals that induce this process have not been fully characterized. Here Yoon et al. identify a signaling complex that instructs actomyosin contractions during apical constriction and show that it is required for neural tube closure.
- Jaeho Yoon
- , Jian Sun
- & Ira O. Daar
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Article
| Open AccessActin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations
Lamin A/C gene mutations cause dilated cardiomyopathy associated with cofilin-1 phosphorylation and actin destabilization. Here, the authors show that phosphorylated cofilin-1 blunts the MRTF-A/SRF axis, leading to decreased tubulin acetylation and altered cardiac structure and function.
- Caroline Le Dour
- , Maria Chatzifrangkeskou
- & Antoine Muchir
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Article
| Open AccessActin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges
The role of actin filaments in clathrin-mediated endocytosis (CME) is unclear. Here, Yang et al. show that branched actin filaments promote CME by pushing on clathrin coat edges in an epsin-dependent manner, dividing large flat clathrin plaques into sizes that facilitate invagination.
- Changsong Yang
- , Patricia Colosi
- & Tatyana Svitkina
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Article
| Open AccessINF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury
Post injury cytoskeletal modifications in neurons are not fully understood. Here the authors describe a pro-survival actin cytoskeletal reorganization in neurons triggered during a model of ischemic stroke.
- Barbara Calabrese
- , Steven L. Jones
- & Shelley Halpain
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Article
| Open AccessTwo Rac1 pools integrate the direction and coordination of collective cell migration
Previous studies suggested a chemokine receptor governed gradient of Rac1 activity is essential for collective guidance of Drosophila border cells. Here, Zhou et al. report that two distinct Rac1 pools at protrusions and cables, not Rac1 activity gradient, integrate the direction and coordination for collective guidance.
- Sijia Zhou
- , Peng Li
- & Xiaobo Wang
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Article
| Open AccessTM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis
F-actin dynamics influence cancer cell motility. Here the authors show that TM9SF4 facilitates the cofilin-induced disassembly of F-actin to promote cancer cell migration and metastasis.
- Zhaoyue Meng
- , Zhichao Li
- & Xiaoqiang Yao
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Article
| Open AccessRab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
The promiscuous GTPase Rab35 has been shown to be involved in many important cellular functions. In this article, Francis et al. illustrate how Rab35 acts as a critical brake to actin remodeling during sprouting angiogenesis and how it is necessary for proper blood vessel development.
- Caitlin R. Francis
- , Hayle Kincross
- & Erich J. Kushner
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Article
| Open AccessIntrinsic cell rheology drives junction maturation
How intrinsic cell properties such as stiffness contribute to cell-cell junction stabilization is not well described. Here they show that higher levels of intrinsic cell mechanics at the cortex, cytoskeleton and nucleus of neighboring cells promote junctional maturation.
- K. Sri-Ranjan
- , J. L. Sanchez-Alonso
- & Vania M. M. Braga
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Article
| Open AccessActin nano-architecture of phagocytic podosomes
Podosomes are actin structures important in multiple cell functions. Here, the authors use iPALM microscopy to reveal an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from it.
- J. Cody Herron
- , Shiqiong Hu
- & Klaus M. Hahn
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Article
| Open AccessMechanism of threonine ADP-ribosylation of F-actin by a Tc toxin
Entomopathogenic bacteria used for pest control secrete potent Tc toxins. Here, the authors combine biochemistry, solution and solid-state NMR spectroscopy and cryo-EM to show in atomic detail how the toxin disrupts the host cell cytoskeleton and kills the target cell.
- Alexander Belyy
- , Florian Lindemann
- & Stefan Raunser
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Article
| Open AccessElasticity of podosome actin networks produces nanonewton protrusive forces
Actin filaments generate force in diverse contexts, although how they can produce nanonewtons of force is unclear. Here, the authors apply cryo-electron tomography, quantitative analysis, and modelling to reveal the podosome core is a dense, spring-loaded, actin network storing elastic energy.
- Marion Jasnin
- , Jordan Hervy
- & Renaud Poincloux
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Article
| Open AccessA glycine-rich PE_PGRS protein governs mycobacterial actin-based motility
Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. Here, Hill & Welch identify an M. marinum surface protein that binds to and activates the host protein NWASP to stimulate actin polymerization and drive bacterial actin-based motility.
- Norbert S. Hill
- & Matthew D. Welch
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Article
| Open AccessBranched actin networks are organized for asymmetric force production during clathrin-mediated endocytosis in mammalian cells
Drubin et al. use three different advanced imaging approaches to show that actin assembles preferentially at stalled clathrin-mediated endocytosis sites, where the actin pulls vesicles into the cell asymmetrically, as a bottle opener pulls off a cap.
- Meiyan Jin
- , Cyna Shirazinejad
- & David G. Drubin
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Article
| Open AccessInhibition of negative feedback for persistent epithelial cell–cell junction contraction by p21-activated kinase 3
Actin and myosin operate at cell–cell junctions during junctional shortening. Here the authors show that prolonged actomyosin contractility can compromise junctional shortening, and that Pak3 is required for attenuation of abnormal active protrusive structure and thus keeps junction contraction, appropriate E-cadherin distribution, and junction shortening in Drosophila.
- Hiroyuki Uechi
- , Kazuki Fukushima
- & Erina Kuranaga
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Article
| Open AccessStructural basis of rapid actin dynamics in the evolutionarily divergent Leishmania parasite
The authors report here the structure-function analysis of highly divergent actin from Leishmania parasite. The study reveals remarkably rapid dynamics of parasite actin as well as the underlying molecular basis, thus providing insight into evolution of the actin cytoskeleton.
- Tommi Kotila
- , Hugo Wioland
- & Pekka Lappalainen
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Article
| Open AccessMechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins
Chemical and mechanical cues coordinately regulate angiogenesis. Here, the authors show that blood flow-driven intraluminal pressure regulates wound angiogenesis. Findings indicate that TOCA family of F-BAR proteins act as actin regulators required for endothelial cell migration and sense mechanical cell stretching to regulate wound angiogenesis.
- Shinya Yuge
- , Koichi Nishiyama
- & Shigetomo Fukuhara
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Article
| Open AccessCalcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure
Calcium serves as an important second messenger in signal transduction to the actin cytoskeleton. Here, we identify EFhD2/Swip-1 as a calcium-dependent actin cross-linker promoting rapid reorganization of actin networks in epithelial wound closure.
- Franziska Lehne
- , Thomas Pokrant
- & Sven Bogdan