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| Open AccessCytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis
Multiciliogenesis requires activation of transcriptional and protein assembly programs; however, the mechanisms that initiate the formation of these multiprotein complexes are unclear. Here the authors show that after inducing centriole biogenesis genes, the transcription factor E2f4 is required in the cytoplasm for assembly and nucleation of deuterosomes.
- Munemasa Mori
- , Renin Hazan
- & Wellington V. Cardoso
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Article
| Open AccessEzrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation
Holes in endothelial barriers, called transendothelial cell macroapertures (TEMs), are predicted to be limited by line tension of unknown origin. Here the authors identify an actomyosin cable encircling TEMs and establish a role for ezrin in stabilising F-actin bundles, allowing their crosslinking by non-muscle myosin IIa.
- Caroline Stefani
- , David Gonzalez-Rodriguez
- & Emmanuel Lemichez
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Article
| Open AccessPrecocious centriole disengagement and centrosome fragmentation induced by mitotic delay
The spindle assembly checkpoint delays mitotic progression until sister chromatids are bi-oriented. Here the authors show that moderate delays in mitotic progression induce centrosome fragmentation and centriole disengagement and that spindle bipolarity is ensured by HSET-mediated spindle pole clustering.
- Menuka Karki
- , Neda Keyhaninejad
- & Charles B. Shuster
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Article
| Open AccessOptogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres
Cellular contractility is regulated by the GTPase RhoA, but how local signals are translated to a cell-level response is not known. Here the authors show that targeted RhoA activation results in propagation of force along stress fibres and actin flow, and identify zyxin as a regulator of stress fibre mechanics and homeostasis.
- Patrick W. Oakes
- , Elizabeth Wagner
- & Margaret L. Gardel
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Article
| Open AccessMyosin-dependent cell-cell communication controls synchronicity of division in acute and chronic stages of Toxoplasma gondii
The mechanism by whichToxoplasma gondiiachieves synchronized cell division is incompletely understood. Here, the authors identify an intravacuolar cell-cell communication that ensures synchronized division and depends on myosin I.
- Karine Frénal
- , Damien Jacot
- & Dominique Soldati-Favre
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Article
| Open AccessMyosin Va molecular motors manoeuvre liposome cargo through suspended actin filament intersections in vitro
Cellular cargo transported along actin filaments is faced with a directional choice at an intersection. Here the authors show that myosin Va-bound cargo prefers to go straight through the intersection, and propose a model to explain this by a tug-of-war between motors on the lipid cargo that engage the actin tracks.
- Andrew T. Lombardo
- , Shane R. Nelson
- & David M. Warshaw
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Article
| Open AccessAn apicobasal gradient of Rac activity determines protrusion form and position
Polarized epithelial cells must correctly position a wide range of subcellular structures. Here the authors demonstrate an apicobasal gradient of Rac GTPase activity, which is maintained by polarity proteins inDrosophilaepithelial sheets, and is required to maintain actin-dependent protrusion form and position.
- Africa Couto
- , Natalie Ann Mack
- & Marios Georgiou
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Article
| Open AccessActin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells
When cells acquire a malignant phenotype they become less stiff and this helps migration and invasion favouring metastasis. Here the authors show that Src-driven cell transformation and transition to a less stiff state follows an event of membrane stiffening due to stress fibres accumulation.
- Sandra Tavares
- , André Filipe Vieira
- & Florence Janody
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Article
| Open AccessActomyosin meshwork mechanosensing enables tissue shape to orient cell force
Large-scale tissue reorganization requires the generation of directional tension, which requires orientation of the cytoskeleton. Here Chanetet al. alter tissue shape and tension in the Drosophilaembryo to show that geometric and mechanical constraints act as cues to orient the cytoskeleton and tension.
- Soline Chanet
- , Callie J. Miller
- & Adam C. Martin
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Article
| Open AccessC. elegans chromosomes connect to centrosomes by anchoring into the spindle network
A connection between centrosomes and chromosomes is a key feature of mitotic spindles. Here the authors generate 3D reconstructions of whole mitotic spindles in earlyC. elegansembryos and show that chromosomes are anchored by the entire spindle network and that connections through kinetochore microtubules are few and likely very transient.
- Stefanie Redemann
- , Johannes Baumgart
- & Thomas Müller-Reichert
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Article
| Open AccessStat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1
Cancer cells have amplified centrosomes and deal with this abnormality by clustering them together so that they can be segregated in daughter cells. Here the authors perform a screening looking for inhibitors of this clustering process and find that STAT3 regulates this process independently of its transcriptional function.
- Edward J. Morris
- , Eiko Kawamura
- & Shoukat Dedhar
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Article
| Open AccessSubnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins
Cilia are hair-like appendages involved in cell motility and sensory reception. Here, the authors report a high resolution cryo-EM structure of the microtubule doublet from motile cilia and identify microtubule inner proteins (MIPs) bound to the inner surface of the doublet that appear to stabilize its structure.
- Muneyoshi Ichikawa
- , Dinan Liu
- & Khanh Huy Bui
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Article
| Open AccessHierarchical assembly of centriole subdistal appendages via centrosome binding proteins CCDC120 and CCDC68
Centriole subdistal appendages (SDAs) anchor microtubules in interphase cells, but their composition and assembly mechanisms are unclear. Here the authors show that two new SDA components, CCDC120 and CCDC68, are required for hierarchical SDA assembly and centrosome microtubule anchoring.
- Ning Huang
- , Yuqing Xia
- & Jianguo Chen
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| Open AccessLocal inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution
Microtubule dynamics are essential for axonal transport. InC. elegans, the authors show that dynein heavy chain regulates the spatial distribution of dendritic microtubules which ensures correct transport progression.
- Shaul Yogev
- , Celine I. Maeder
- & Kang Shen
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Article
| Open AccessAnisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration
Contact guidance on aligned substrates leads to directed cell migration through a poorly defined mechanism. Here the authors show that alignment of adhesion structures and F-actin generates anisotropic traction stress to drive directional migration, and cell-cell contact reduces force orientation and directional response.
- Arja Ray
- , Oscar Lee
- & Paolo P. Provenzano
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Article
| Open AccessCrystal structure of Zen4 in the apo state reveals a missing conformation of kinesin
Kinesins are molecular motors that travel along microtubules through a nucleotide-dependent stepping mechanism. Here the authors present the crystal structure of Zen4 (kinesin-6) in an apo state that sheds light on a key stepping intermediate of kinesin.
- Ruifang Guan
- , Lei Zhang
- & Zhucheng Chen
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Article
| Open AccessLoss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease
ARPC1B is a component of the actin-related protein 2/3 complex (Arp2/3), which is required for actin filament branching. Kahret al. show that ARPC1B deficiency in humans is associated with severe multisystem disease that includes platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.
- Walter H. A. Kahr
- , Fred G. Pluthero
- & Aleixo M Muise
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Article
| Open AccessRole for formin-like 1-dependent acto-myosin assembly in lipid droplet dynamics and lipid storage
Lipid droplets (LDs) are cellular organelles dedicated to triacylglycerol storage that can undergo fusion and dissociation events. Here the authors show that formin-like 1-dependent acto-myosin assembly on LDs facilitates their dissociation and, as a consequence, affects hydrolysis and storage of triacylglycerols.
- Simon G. Pfisterer
- , Gergana Gateva
- & Elina Ikonen
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| Open AccessCell-free reconstitution reveals centriole cartwheel assembly mechanisms
The centriole is an organelle composed of rings of SAS-6 proteins that form a cartwheel structure. Here the authors develop a cell-free system to examine core cartwheel assembly ofC. reinhardtiiproteins and discover that CrSAS-6 has autonomous properties that facilitates self-organized stacking of pairs of rings.
- P. Guichard
- , V. Hamel
- & P. Gönczy
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Article
| Open AccessFMNL formins boost lamellipodial force generation
Actin polymerization in lamellipodia of cells is regulated by the Arp2/3 complex and FMNL family formins. Here the authors show that both FMNL2 and FMNL3 contribute to lamellipodium protrusion and structure, and abolishing FMNL2/3 reduces protrusion force generation and migration, without affecting Arp2/3 incorporation.
- Frieda Kage
- , Moritz Winterhoff
- & Klemens Rottner
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Article
| Open AccessProbing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots
Methods to probe transport dynamics within cells can shed insight into the nature of the cytoplasm. Here the authors develop a method to functionalize and deliver quantum dots intracellularly to show how the cytoskeleton influences non-equilibrium intracellular transport dynamics.
- Eugene A. Katrukha
- , Marina Mikhaylova
- & Lukas C. Kapitein
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| Open AccessDeconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention
Buparlisib/BKM120 is in phase 3 clinical trials as a phosphoinositide 3-kinase (PI3K) inhibitor. Here, Bohnackeret al. combine chemical biology and structural biology approaches to segregate BKM120’s biological actions, and suggest that it causes mitotic arrest predominantly by binding microtubules and disrupting their dynamics.
- Thomas Bohnacker
- , Andrea E. Prota
- & Matthias P. Wymann
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| Open AccessEnsemble and single-molecule dynamics of IFT dynein in Caenorhabditis elegans cilia
Cytoplasmic dynein 2 drives retrograde intraflagellar transport but little is known about its dynamics. Here the authors use fluorescence microscopy to track labelled dynein 2 inC. elegansat the single-molecule level and report diffusion at the ciliary base, and pausing and directional switches along the cilium.
- Jona Mijalkovic
- , Bram Prevo
- & Erwin J. G. Peterman
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| Open AccessDrebrin-mediated microtubule–actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection
Neuronal migration is vital for neuronal circuit morphogenesis and is thought to rely on microtubule-actomyosin crosstalk. Here, the authors use super-resolution imaging and the drebrin microtubule-actin crosslinking protein to show that microtubule-actomyosin coupling controls the direction of centrosome and somal motility.
- Niraj Trivedi
- , Daniel R. Stabley
- & David J. Solecki
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Article
| Open AccessOxidation of F-actin controls the terminal steps of cytokinesis
Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.
- Stéphane Frémont
- , Hussein Hammich
- & Arnaud Echard
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Article
| Open AccessSelf-organizing actin patterns shape membrane architecture but not cell mechanics
In vitro models of actin organization show the formation of vortices, asters and stars. Here Fritzsche et al. show that such actin structures form in living cells in a manner dependent on the Arp2/3 complex but not myosin, and such structures influence membrane architecture but not cortex elasticity.
- M. Fritzsche
- , D. Li
- & C. Eggeling
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Article
| Open AccessOptogenetic control of cellular forces and mechanotransduction
Cellular mechanical forces are regulated by Rho GTPases. Here the authors develop an optogenetic system to control the spatiotemporal activity of RhoA, and show that directing a RhoA activator to the plasma membrane causes contraction and YAP nuclear localization, whereas directing it to the mitochondria causes relaxation.
- Léo Valon
- , Ariadna Marín-Llauradó
- & Xavier Trepat
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| Open AccessKIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling
The ciliary transition zone (TZ) regulates the protein and membrane composition of the primary cilium. Here the authors identify the kinesin-3 motor protein KIF13B as a regulator of TZ membrane composition that controls the ciliary accumulation of Smoothened, which is involved in activation of Sonic hedgehog signalling.
- Kenneth B. Schou
- , Johanne B. Mogensen
- & Lotte B. Pedersen
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Article
| Open AccessRhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.
- Thiviyani Maruthappu
- , Anissa Chikh
- & David P. Kelsell
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Article
| Open AccessGlucocorticoid receptor signalling activates YAP in breast cancer
Activation of YAP contributes to tumorigenesis in several tissues. Here, the authors show that in breast cancer cells glucocorticoids induce expression of fibronectin that in turn activates focal adhesion kinase/Src signalling to promote YAP nuclear translocation and transcriptional activity.
- Giovanni Sorrentino
- , Naomi Ruggeri
- & Giannino Del Sal
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| Open AccessExpression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses
The assembly of the first centrosome occurs upon fertilisation when male centrioles recruit pericentriolar material from the egg cytoplasm. Here the authors identify Wdr8 as a maternally essential protein that is required for centrosome assembly during embryonic mitoses of medaka.
- Daigo Inoue
- , Manuel Stemmer
- & Oliver J. Gruss
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| Open AccessThe mitotic kinesin-14 KlpA contains a context-dependent directionality switch
Kinesin-14s are commonly considered to be minus end-directed microtubule motor proteins. Here the authors show that KlpA, a fungal kinesin-14 orthologue, relies on its N-terminal nonmotor microtubule-binding tail to achieve context-dependent bidirectional motility.
- Andrew R. Popchock
- , Kuo-Fu Tseng
- & Weihong Qiu
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| Open AccessTwo pathways regulate cortical granule translocation to prevent polyspermy in mouse oocytes
Mammalian eggs release cortical granules to avoid being fertilized by more than a single sperm as polyspermy results in nonviable embryos. Here, the authors describe the mechanism driving translocation of the granules to the cortex in the mouse egg and show this process is essential to prevent polyspermy.
- Liam P. Cheeseman
- , Jérôme Boulanger
- & Melina Schuh
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Article
| Open AccessActin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins
The ExoY toxin is injected by Pseudomonas aeruginosainto host cells, where it is activated by an unknown host factor. Here the authors identify such factor as filamentous actin.
- Alexander Belyy
- , Dorothée Raoux-Barbot
- & Undine Mechold
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Article
| Open AccessAutophagy controls centrosome number by degrading Cep63
The ubiquitin-proteasome system is thought to be the primary regulator of centrosome number. Here, Watanabe et al. show that selective autophagy also plays a role in regulating centrosome number via p62-dependent recruitment of centrosomal protein 63 to autophagosomes.
- Yuichiro Watanabe
- , Shinya Honda
- & Shigeomi Shimizu
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Article
| Open AccessMicrotubule organization is determined by the shape of epithelial cells
Interphase microtubule organization creates a structural scaffold for cargo delivery determining cell polarity and cell shape. Here the authors show that in Drosophilaepithelia the orientation of microtubules responds to cell shape, rather than the converse, and develop a simple model to mimic this behaviour.
- Juan Manuel Gomez
- , Lyubov Chumakova
- & Nicholas H. Brown
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Article
| Open AccessBoundaries steer the contraction of active gels
The actomyosin cytoskeleton consists of a contractile array but how it becomes organized is not clear. Here the authors reconstitute a controllable contractile system to show that force balances at boundaries determine contraction dynamics, and spatial anisotropy leads to self-organization or aligned contractile fibres.
- Matthias Schuppler
- , Felix C. Keber
- & Andreas R. Bausch
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Article
| Open AccessActomyosin-dependent dynamic spatial patterns of cytoskeletal components drive mesoscale podosome organization
Podosomes are adhesive cytoskeletal structures found in several cell types, but whether or how they are interconnected is not known. Here the authors demonstrate mesoscale connectivity of podosome clusters by imaging directional flow patterns of podosome components vinculin, talin and F-actin.
- Marjolein B. M. Meddens
- , Elvis Pandzic
- & Alessandra Cambi
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Article
| Open AccessCoordinated integrin activation by actin-dependent force during T-cell migration
The role of force in activating integrin cell adhesion receptors is not known. Here the authors develop fluorescent tension sensors for αL and β2 integrins and show that in migrating T cells force is transduced across the β2 integrin, and that this correlates with an active conformational state.
- Pontus Nordenfelt
- , Hunter L. Elliott
- & Timothy A. Springer
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Article
| 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 AccessTransport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity
Transport of cargo into dendritic spines is required for synaptic plasticity. McVicker et al.describe a method of activity-dependent transport of a kinesin KIF1A and its cargo synaptotagmin-IV along microtubules that are transiently polymerized into dendritic spines.
- Derrick P. McVicker
- , Adam M. Awe
- & Erik W. Dent
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Article
| Open AccessCortical dynamics during cell motility are regulated by CRL3KLHL21 E3 ubiquitin ligase
Although focal adhesions (FAs) and microtubules (MTs) are known to associate, the underlying regulation of this dynamic interaction is not understood. Here the authors discover that the CRL3KLHL21E3 ubiquitin ligase localises to FAs and ubiquitinates the MT plus-tip binding protein EB1, thereby promoting MT and FA dynamics and cell migration.
- Thibault Courtheoux
- , Radoslav I. Enchev
- & Matthias Peter
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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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Article
| Open AccessA centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4
The centrosome is a large intracellular structure that serves as the microtubule-organising center, but how it is accurately assembled is not known. Here the authors generate a ‘domain-level’ centrosome interactome and show that Plk4 positions the essential centriole component Asterless by phosphorylating Cep135.
- Brian J. Galletta
- , Carey J. Fagerstrom
- & Nasser M. Rusan
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Article
| Open AccessSevere NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages
Human mutations in the NDE1 gene have been associated with cortical malformations and severe microcephaly. Here, the authors show in embryonic rat brains that NDE1-depleted neural progenitors arrest at three specific cell cycle stages before mitosis, resulting in a severe decrease in neurogenesis.
- David J. Doobin
- , Shahrnaz Kemal
- & Richard B. Vallee
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Article
| 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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Article
| Open AccessTau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
Tau, an intrinsically disordered axonal protein, binds to and regulates microtubule dynamics. Here, the authors use SAXS and electron microscopy to examine the architectures of microtubule bundles, including those mimicking microtubule fascicles in the axon initial segment.
- Peter J. Chung
- , Chaeyeon Song
- & Cyrus R. Safinya
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Article
| 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