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| Open AccessDirect binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly
Centriole duplication is tightly regulated in vivo, but the underlying molecular mechanisms are incompletely understood. Here the authors use high-resolution structural and imaging methods to show that CEP85 directly interacts with STIL and mediates efficient centriolar targeting of STIL, PLK4 activation and centriole assembly.
- Yi Liu
- , Gagan D. Gupta
- & Mark van Breugel
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Article
| Open AccessTAK1 activation of alpha-TAT1 and microtubule hyperacetylation control AKT signaling and cell growth
Acetylation of microtubules (MT) confers mechanical stability necessary for numerous cellular functions but its regulation is unclear. Here the authors show that the MT acetyltransferase αTAT1 is regulated by TGF-β-activated kinase 1 implicating TGF-β signaling in MT-related functions and disease.
- Nirav Shah
- , Sanjay Kumar
- & Nam Y. Lee
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Article
| Open AccessCryo-EM reveals the structural basis of microtubule depolymerization by kinesin-13s
Kinesin-13s are microtubule depolymerases that lack motile activity. Here the authors present the cryo-EM structures of kinesin-13 microtubule complexes in different nucleotide bound states, which reveal how ATP hydrolysis is linked to conformational changes and propose a model for kinesin induced depolymerisation.
- Matthieu P.M.H. Benoit
- , Ana B. Asenjo
- & Hernando Sosa
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Article
| Open AccessCapping protein-controlled actin polymerization shapes lipid membranes
Cell membrane protrusions and invaginations are both driven by actin assembly but the mechanism leading to different membrane shapes is unknown. Using a minimal system and modelling the authors reconstitute the deformation modes and identify capping protein as a regulator of both deformation types.
- Katharina Dürre
- , Felix C. Keber
- & Andreas R. Bausch
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Article
| Open AccessCompetition between microtubule-associated proteins directs motor transport
Motor and non-motor microtubule-associated proteins (MAPs) bind to the microtubule lattice, but it is unclear how their binding activities are coordinated and how this impacts motor transport. Here the authors show how MAP competition controls microtubule access to determine the distribution and balance of motor activity.
- Brigette Y. Monroy
- , Danielle L. Sawyer
- & Kassandra M. Ori-McKenney
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Article
| Open AccessSrf destabilizes cellular identity by suppressing cell-type-specific gene expression programs
The transcription factor Srf is a central regulator of immediate-early and actin cytoskeletal genes. Here the authors show that Srf is activated by repression of β-actin, promoting iPSC reprogramming of neural progenitor cells and hepatoblasts by repressing cell-type specific genes.
- Takashi Ikeda
- , Takafusa Hikichi
- & Shinji Masui
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Article
| Open AccessOver-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation
Cancer cells are characterised by abnormalities in the number of centrosomes and this phenotype is linked with tumorigenesis. Here the authors report centriole length deregulation in a subset of cancer cell lines and suggest a link with subsequent alterations in centriole numbers and chromosomal instability.
- Gaëlle Marteil
- , Adan Guerrero
- & Mónica Bettencourt-Dias
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Article
| Open AccessThe CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by targeting STAT1 for degradation
Intu is a planar cell polarity protein known to regulate ciliogenesis during embryonic development. Here, Wang et al. identify a role for Intu in adult kidneys, where they find it promotes degradation of STAT1 and thus prevents cilia loss and cell death upon ischemia-reperfusion injury.
- Shixuan Wang
- , Aimin Liu
- & Zheng Dong
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Article
| Open AccessA biochemical network controlling basal myosin oscillation
The actomyosin cytoskeleton is known to spontaneously oscillate in many systems but the mechanism of this behavior is not clear. Here Qin et al. define a signaling network involving a ROCK-dependent self-activation loop and recruitment of myosin II to the cortex, followed by a local accumulation of myosin phosphatase that shuts off the signal.
- Xiang Qin
- , Edouard Hannezo
- & Xiaobo Wang
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Article
| Open AccessThe preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor
Land plants lack the cytoplasmic dynein motor in fungi and animals that shows processive minus-end-directed motility on microtubules. Here the authors demonstrate that land plants have evolved novel processive minus-end-directed kinesin-14 motors that likely compensate for the absence of dynein.
- Kuo-Fu Tseng
- , Pan Wang
- & Weihong Qiu
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Article
| Open AccessDesmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination
The epidermis is a multi-layered epithelium formed by the differentiation of basal cells and movement into suprabasal layers. Here the authors define a role for the desmosomal cadherin desmoglein-1 in promoting the delamination of basal cells by remodeling the actin cytoskeleton through interactions with the dynein light chain Tctex-1 and cortactin.
- Oxana Nekrasova
- , Robert M. Harmon
- & Kathleen J. Green
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Article
| Open Accessp63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response
Mutations in the gene encoding iRHOM2 are associated with hyperproliferative epidermal disorders. Here, the authors show that iRHOM2 is a target gene of p63, that together they regulate inflammation, cell survival and response to oxidative stress, and inhibition of p63-iRHOM2 signalling with an antioxidant reduces epidermal inflammation.
- Paola Arcidiacono
- , Catherine M. Webb
- & Anissa Chikh
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Article
| Open AccessAn HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Vascular smooth muscle cell (VSMC) dysfunction is a common feature of thoracic aortic aneurysms (TAAs). Here, Lino Cardenas and colleagues show that the formation of a HDAC9-MALAT1-BRG1 complex promotes VSMC dysfunction in TAA by epigenetically altering the expression of key components of the cytoskeleton in VSMCs.
- Christian L. Lino Cardenas
- , Chase W. Kessinger
- & Mark E. Lindsay
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Article
| Open AccessA conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity
A growing number of cargo-specific effector proteins are being identified that interact with both dynein and dynactin and form processive dynein-dynactin-effector complexes. Here the authors identify and characterize a conserved mechanism of interaction between dynein and unrelated effector proteins.
- In-Gyun Lee
- , Mara A. Olenick
- & Roberto Dominguez
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Article
| Open AccessUncovering the balance of forces driving microtubule aster migration in C. elegans zygotes
Microtubule asters are positioned precisely within cells by forces generated by molecular motors, but it is unclear how these are integrated in space and time. Here the authors perform in vivo drag measurements and genetic manipulations to determine the balance of forces that position microtubule asters in C. elegans zygotes.
- A. De Simone
- , A. Spahr
- & P. Gönczy
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Article
| Open AccessA peptide tag-specific nanobody enables high-quality labeling for dSTORM imaging
Nanobodies (Nbs) coupled to organic dyes are increasingly used for super-resolution cell imaging, but producing gene-specific Nbs is time-consuming. Here the authors present a peptide-tag/Nb combination for dSTORM imaging which can be easily adapted to different targets in fixed and live cells.
- David Virant
- , Bjoern Traenkle
- & Ulrich Rothbauer
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Article
| Open AccessSingle cell polarity in liquid phase facilitates tumour metastasis
Polarisation of metastasising cancer cells in circulation has not been investigated before. Here the authors identify single cell polarity as a distinct polarisation state of single cells in liquid phase, and show that perturbing single cell polarity affects attachment, adhesion, transmigration and metastasis in vitro and in vivo.
- Anna Lorentzen
- , Paul F. Becker
- & Mathias Heikenwalder
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Article
| Open AccessEGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase
The trichoplein-Aurora A pathway inhibits ciliogenesis in proliferating cells. Here the authors EGFR-mediated phosphorylation of the deubiquitinating enzyme USP8 leads to its activation, and this suppresses trichoplein degradation, allowing inhibition of ciliogenesis.
- Kousuke Kasahara
- , Hiromasa Aoki
- & Masaki Inagaki
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Article
| Open AccessMutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human
Asthenozoospermia is a major cause of male infertility, and multiple morphological abnormalities of the flagella (MMAF) is a particularly severe form. Here, using whole-exome sequencing of 78 MMAF patients, the authors identify mutations in two WDR proteins, CFAP43 and CFAP44, and confirm that these proteins are required for flagellogenesis in mouse and Trypanosoma brucei.
- Charles Coutton
- , Alexandra S. Vargas
- & Pierre F. Ray
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Article
| Open AccessLymphocyte-specific protein 1 regulates mechanosensory oscillation of podosomes and actin isoform-based actomyosin symmetry breaking
The actomyosin cytoskeleton plays an important role in polarised cell migration. Here the authors identify lymphocyte-specific protein (LSP)-1 as a regulator of actomyosin contractility in macrophages, by competing with supervillin for myosin IIA activators acting specifically on the β-actin isoform.
- Pasquale Cervero
- , Christiane Wiesner
- & Stefan Linder
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Article
| Open AccessMembrane shape-mediated wave propagation of cortical protein dynamics
Traveling waves in the cell cortex can propagate much faster than actin waves, and the mechanism is unknown. Here the authors propose a mechanochemical feedback model for traveling waves that incorporates membrane shape changes and recruitment of F-BAR proteins that enables fast wave propagation.
- Zhanghan Wu
- , Maohan Su
- & Jian Liu
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Article
| Open AccessA conserved ankyrin repeat-containing protein regulates conoid stability, motility and cell invasion in Toxoplasma gondii
Apicomplexan parasites such as Toxoplasma gondii possess a tubulin-rich structure called the conoid. Here, Long et al. identify a conoid protein that interacts with motor and structural proteins and is required for structural integrity of the conoid, parasite motility, and host cell invasion.
- Shaojun Long
- , Bryan Anthony
- & L. David Sibley
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Article
| Open AccessThe HIV co-receptor CCR5 regulates osteoclast function
CCR5 is a co-receptor for HIV, and loss of function is associated with lower incidence of HIV but also with bone-destructive diseases. Here the authors show that ablation of CCR5 impairs osteoclast function and improves resistance to osteoporosis in mouse models.
- Ji-Won Lee
- , Akiyoshi Hoshino
- & Tadahiro Iimura
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Article
| Open AccessShe1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain
Dynein is a microtubule motor the motility of which is affected by the microtubule-associated protein She1. Here, the authors show that She1 alters dynein stepping behavior and increases its microtubule affinity through simultaneous interactions with the microtubule and dynein microtubule binding domain.
- Kari H. Ecklund
- , Tatsuya Morisaki
- & Steven M. Markus
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Article
| Open AccessNuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology
An actin cap protects the morphology of the nucleus during cellular mechanical stress. Here, the authors show that the nuclear lamina protein lamin A/C mediates the formation of the actin cap in response to stress, and model the distribution of forces in the presence and absence of the actin cap.
- Jeong-Ki Kim
- , Arghavan Louhghalam
- & Dong-Hwee Kim
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Article
| Open AccessNucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics
Microtubules are vital and highly conserved components of the cytoskeleton. Here the authors carry out a structural analysis of fission yeast microtubules in the presence and absence of the microtubule end-binding protein Mal3 that demonstrates structural plasticity amongst microtubule polymers.
- Ottilie von Loeffelholz
- , Neil A. Venables
- & Carolyn A. Moores
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Article
| Open AccessDirection of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here the authors show that actin flow can orient cell surface integrins during leukocyte migration, suggesting integrin activation by cytoskeletal force.
- Pontus Nordenfelt
- , Travis I. Moore
- & Timothy A. Springer
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Article
| Open AccessIFT proteins spatially control the geometry of cleavage furrow ingression and lumen positioning
Cytokinesis relies on central spindle organization and provides a spatial landmark for lumen formation. Here, the authors show that intraflagellar transport proteins are required for the localization of the cytokinetic regulator Aurora B and subsequent cleavage furrow ingression and lumen positioning.
- Nicolas Taulet
- , Benjamin Vitre
- & Benedicte Delaval
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Article
| Open AccessInduced cortical tension restores functional junctions in adhesion-defective carcinoma cells
Cancer cells can disrupt cell-to-cell junctions, thus allowing migration and metastasis. Here starting from a chemical screening, Ito et al. reconstitute a step-by-step mechanism linking microtubule depolymerization and epithelial cell junction restoration.
- Shoko Ito
- , Satoru Okuda
- & Masatoshi Takeichi
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Article
| Open AccessBactofilin-mediated organization of the ParABS chromosome segregation system in Myxococcus xanthus
The roles played by bactofilins, a widespread type of bacterial cytoskeletal elements, are unclear. Here, the authors show that the bactofilins BacNOP facilitate proper subcellular localization of the ParABS chromosome segregation system in the model organism Myxococcus xanthus.
- Lin Lin
- , Manuel Osorio Valeriano
- & Martin Thanbichler
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Article
| Open AccessCritical role of the HDAC6–cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect
Histone deacetylase (HDAC) inhibitors, a class of cancer therapeutics, cause thrombocytopenia via an unknown mechanism. Here, the authors show that HDAC6 inhibition impairs proplatelet formation in human megakaryocytes, and show that this is linked to hyperacetylation of the actin-binding protein cortactin.
- Kahia Messaoudi
- , Ashfaq Ali
- & Najet Debili
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Article
| Open AccessR-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature
Formation of the vascular lumen initiates the blood flow and it is crucial for tissue homeostasis. Here, Li et. al show that the R-Ras-Akt signaling axis is crucial for reparative angiogenesis in mice because it stabilizes the microtubule cytoskeleton in endothelial cells to promote endothelial lumen formation.
- Fangfei Li
- , Junko Sawada
- & Masanobu Komatsu
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Article
| Open AccessmDia1 senses both force and torque during F-actin filament polymerization
Formins are actin-polymerisation factors that are sensitive to force. Here the authors find that pulling force on an actin filament promoted faster actin polymerisation by the formin mDia1, and also found that the actin filament must be torsionally unconstrained, suggesting that mDia1 can also sense torque.
- Miao Yu
- , Xin Yuan
- & Jie Yan
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Article
| Open AccessWiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells
Wiskott-Aldrich syndrome protein (WASp) is essential for controlling the cytoskeleton, but its function in innate immunity is unclear. Here the authors show that WASp deficiency is associated with dysregulated septin cage formation, excessive inflammasome activation, elevated immune cell death and reduced bacterial clearance.
- Pamela P. Lee
- , Damián Lobato-Márquez
- & Adrian J. Thrasher
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Article
| Open AccessCytokinesis requires localized β-actin filament production by an actin isoform specific nucleator
Cytokinesis is initiated by the localized assembly of the contractile ring. Here the authors show that the stabilization and organization of the cytokinetic furrow requires localized β-actin filament assembly at the site of cytokinesis by an actin isoform specific nucleator.
- A. Chen
- , P. D. Arora
- & A. Wilde
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Article
| Open AccessActive diffusion and advection in Drosophila oocytes result from the interplay of actin and microtubules
Intracellular transport is facilitated by a combination of processes including directed transport, advection and diffusion. Here the authors microscopically characterise the dynamics of the Drosophila oocyte and find distinct contributions of cytoskeletal components to advection and active diffusion.
- Maik Drechsler
- , Fabio Giavazzi
- & Isabel M. Palacios
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Article
| Open AccessChromosome segregation occurs by microtubule pushing in oocytes
In oocytes of most species atypical spindles assembled in the absence of centrosomes drive chromosome segregation, however the forces driving this process are unclear. Here the authors found that spindle poles are largely dispensable and that inter-chromosomal microtubules of the central spindle control chromosomal segregation.
- Kimberley Laband
- , Rémi Le Borgne
- & Julien Dumont
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Article
| Open AccessLeucine repeat adaptor protein 1 interacts with Dishevelled to regulate gastrulation cell movements in zebrafish
Gastrulation is an early morphogenic event driven by coordinated asymmetric/polarised cell movements. Here, the authors show in zebrafish that Lurap1, a protein that interacts with Dishevelled, regulates Wnt and planar cell polarity, coordinating centriole positioning during convergence and extension.
- Xiao-Ning Cheng
- , Ming Shao
- & De-Li Shi
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Article
| Open AccessActomyosin pulsation and flows in an active elastomer with turnover and network remodeling
Tissue remodeling involves substantial involvement of the contractile actomyosin cytoskeleton. Here the authors model the spatiotemporal evolution of actomyosin densities during Drosophila germband extension and find affine and nonaffine deformations that depend on the magnitude of local contractile stress.
- Deb Sankar Banerjee
- , Akankshi Munjal
- & Madan Rao
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Article
| Open AccessThe giant protein titin regulates the length of the striated muscle thick filament
Thick filaments in skeletal muscle and heart are composed of myosin. The authors show that the length of thick filaments is defined by titin, and that alterations in titin length affect force generation and lead to dilated cardiomyopathy in mice.
- Paola Tonino
- , Balazs Kiss
- & Henk Granzier
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Article
| Open AccessApical surface supracellular mechanical properties in polarized epithelium using noninvasive acoustic force spectroscopy
Determination of apical tension, fluidity, and intercellular adhesive forces in an epithelial monolayer are currently disruptive. Here the authors present a method using acoustic force microscopy to measure changes in these parameters upon tight junction structural alterations in a MDCK monolayer.
- Alexander X. Cartagena-Rivera
- , Christina M. Van Itallie
- & Richard S. Chadwick
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Article
| Open AccessActomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse embryo
The molecular trigger that establishes cell polarity in the mammalian embryo is unclear. Here, the authors show that de novo polarisation of the mouse embryo at the 8-cell stage is directed by Phospholipase C and Protein kinase C and occurs in two phases: polarisation of actomyosin followed by the Par complex.
- Meng Zhu
- , Chuen Yan Leung
- & Magdalena Zernicka-Goetz
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Article
| Open AccessExtracellular matrix stiffness and cell contractility control RNA localization to promote cell migration
Adenomatous polyposis coli (APC) regulates the localization of some mRNAs at cellular protrusions but the underlying mechanisms and functional roles are not known. Here the authors show that APC-dependent RNAs are enriched in contractile protrusions, via detyrosinated microtubules, and enhance cell migration.
- Tianhong Wang
- , Susan Hamilla
- & Stavroula Mili
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Article
| Open AccessMechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly
The fission yeast cytokinetic ring assembles by Search-Capture-Pull-Release from precursor nodes that include formin Cdc12 and myosin Myo2. The authors reconstitute Search-Capture-Pull in vitro and find that Myo2 pulling on Cdc12-associated actin filaments mechano-inhibits Cdc12-mediated assembly, which enables proper ring assembly in vivo.
- Dennis Zimmermann
- , Kaitlin E. Homa
- & David R. Kovar
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Article
| Open AccessNetwork heterogeneity regulates steering in actin-based motility
Protrusive cellular structures contain a heterogeneous density of actin, but whether this influences motility is not known. Using an in vitro system and modelling, here the authors show that local actin monomer depletion and network architecture can tune the rate of network growth to impose steering during motility.
- Rajaa Boujemaa-Paterski
- , Cristian Suarez
- & Laurent Blanchoin
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Article
| Open AccessThe catalytic subunit of DNA polymerase δ inhibits γTuRC activity and regulates Golgi-derived microtubules
Microtubule organization requires γ-tubulin ring complexes (γTuRCs), but the mechanisms that control γTuRC-mediated microtubule nucleation are unclear. Here the authors show that the DNA polymerase δ catalytic subunit controls noncentrosomal γTuRC activity and regulates the organization of Golgi-derived microtubules.
- Yuehong Shen
- , Pengfei Liu
- & Robert Z. Qi
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Article
| Open AccessHuman microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles
- Hsin-Yi Chen
- , Chien-Ting Wu
- & Tang K. Tang
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Article
| Open AccessActomyosin drives cancer cell nuclear dysmorphia and threatens genome stability
Recent findings suggest that forces acting on the cell nucleus can cause DNA damage, but the mechanisms are unclear. Here Takakiet al. report that actomyosin is a determinant of nuclear shape and that unrestrained contractility elicits nuclear envelope rupture and genome instability in cancer cells.
- Tohru Takaki
- , Marco Montagner
- & Mark Petronczki
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Article
| Open AccessFlat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors
Clathrin lattices coat flat membrane regions, called plaques, whose regulation and function are poorly understood. Here the authors find that plaques are regulated by actin dynamics and contain both the endocytic and the cell adhesion machineries, and are involved in endocytosis of specific cargos, and cell migration.
- Daniela Leyton-Puig
- , Tadamoto Isogai
- & Metello Innocenti