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| Open AccessConserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein
The mechanism by which dynein-mediated cargo transport is switched on is unresolved. This study reveals insights into the roles of the human disease genes Ndel1 and LIS1 in the assembly and activation of dynein transport complexes.
- Kyoko Okada
- , Bharat R. Iyer
- & Richard J. McKenney
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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 AccessFAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction
Microtubule inner proteins (MIPs) contribute to species-specific motility characteristics but are largely unstudied. Here, the authors combine functional, structural and proteomic analysis in T. brucei to advance fundamental understanding of MIP assembly and identify trypanosome-specific MIPs required for motility.
- Michelle M. Shimogawa
- , Angeline S. Wijono
- & Kent L. Hill
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Article
| Open AccessControl of motor landing and processivity by the CAP-Gly domain in the KIF13B tail
Intracellular transport of material along microtubules by kinesin motors is critical for cellular homeostasis. Here the authors uncover a unique role for a specialized kinesin tail domain in directing motor transport along specific microtubule tracks.
- Xiangyu Fan
- & Richard J. McKenney
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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 AccessAcentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Microtubules need to be generated during cell division to build mitotic or meiotic spindles. Here, reconstitution experiments and theoretical modeling show that chromosomes alone can trigger branching microtubule nucleation.
- Bernardo Gouveia
- , Sagar U. Setru
- & Sabine Petry
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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 AccessMuscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes
RNA localization is mediated by kinesin motors and anchoring. However, mechanisms underlying specificity are unclear. Here, the authors find that MBNL protein’s zinc fingers prefer specific kinesins, and its unstructured tail mediates membrane anchoring.
- Ryan P. Hildebrandt
- , Kathryn R. Moss
- & Eric T. Wang
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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 AccessHydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures
Organ-like 3D cultures are advanced model system for biology and medicine limited by their uncontrolled cell self-assembly. Here, the authors develop a hydrogel-in-hydrogel bioprinting approach to dynamically control the growth landscape of a broad range of living 3D cell cultures.
- Anna Urciuolo
- , Giovanni Giuseppe Giobbe
- & Nicola Elvassore
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Article
| Open AccessApicobasal RNA asymmetries regulate cell fate in the early mouse embryo
How do cells of the preimplantation mouse embryo make decisions? Here the authors discovered that the spatial sorting of mRNAs, tRNA, rRNAs and organelles lead to localized translation, conducive for cell fate allocation and embryonic development.
- Azelle Hawdon
- , Niall D. Geoghegan
- & Jennifer Zenker
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Article
| Open AccessThe nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization
Contractile forces are key to sorting the embryonic inner cell mass from the extraembryonic trophectoderm. Here they show that Lamin-A links changes in mechanical forces to cell fate specification, enabling Yap-Cdx2 signaling in outer, but not inner cells.
- Robin M. Skory
- , Adam A. Moverley
- & Nicolas Plachta
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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 AccessAMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration
Cell metabolism must adapt to the energy needs of migrating cells. This study finds that fast amoeboid migrating cells harbor high AMPK activity, which controls both mitochondrial dynamics and cytoskeletal remodeling, enabling reduced energy needs.
- Eva Crosas-Molist
- , Vittoria Graziani
- & Victoria Sanz-Moreno
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Article
| Open AccessEB1 decoration of microtubule lattice facilitates spindle-kinetochore lateral attachment in Plasmodium male gametogenesis
EB are conserved microtubule (MT) plus-end binding proteins. Here, Yang et al. report that Plasmodium EB1 possesses distinct MT-lattice affinity and decorates the full-length of spindle MTs. Gene deletion impairs the spindle-kinetochore lateral attachment, leading to anucleated male gametes.
- Shuzhen Yang
- , Mengya Cai
- & Jing Yuan
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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 AccessBICD2 phosphorylation regulates dynein function and centrosome separation in G2 and M
The dynein motor complex has a variety of important functions in both dividing and non-dividing cells. Here, Gallisà et al. describe a mode of regulation of dynein based on the phosphorylation of its adaptor BICD2 by the kinase PLK1, and how this is central for the regulation of centrosome position in G2 and M.
- Núria Gallisà-Suñé
- , Paula Sànchez-Fernàndez-de-Landa
- & Joan Roig
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Article
| Open AccessNative doublet microtubules from Tetrahymena thermophila reveal the importance of outer junction proteins
Using cryo-EM, the authors identified 42 MIPs, including outer junction protein CFAP77 and outer dense fibers, in native doublet microtubules of Tetrahymena thermophila. Knockout of CFAP77 reduced ciliary beat frequency and led to outer junction damage.
- Shintaroh Kubo
- , Corbin S. Black
- & Khanh Huy Bui
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| Open AccessStructural insights into how augmin augments the mitotic spindle
Cell division critically requires amplification of microtubules (MTs) in the bipolar mitotic spindle. This relies on the filamentous augmin complex that enables MT branching. Studies by Gabel et al., Zupa et al. and Travis et al. describe consistent integrated atomic models of the extraordinarily flexible augmin complex. Their work prompts the question: what is this flexibility really needed for?
- Szymon W. Manka
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Article
| Open AccessIntegrated model of the vertebrate augmin complex
Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
- Sophie M. Travis
- , Brian P. Mahon
- & Sabine Petry
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Article
| Open AccessA stress-induced cilium-to-PML-NB route drives senescence initiation
Exposure to irreparable stresses induces transient ciliogenesis, enabling communication with PML-NBs via a FBF1 pathway to trigger senescence in mammalian cells. Fbf1 ablation reduces senescence and associated health decline in mice, highlighting cilia as a promising senotherapy target.
- Xiaoyu Ma
- , Yingyi Zhang
- & Jinghua Hu
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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 AccessDistinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity
Male meiosis relies on canonical centrosomes for spindle formation, but how this differs from acentrosomal oocyte meiosis is unclear. Here they show that spindle formation in sperm relies on DYNLRB2, similar to the activity of DYNLRB1 in mitotic cells.
- Shuwen He
- , John P. Gillies
- & Hiroki Shibuya
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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 AccessMena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.
- Frederic Li Mow Chee
- , Bruno Beernaert
- & Adam Byron
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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 AccessTRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport
The mechanisms of microtubule-based mitochondrial transport remain poorly understood. Here, the authors show that the mitochondrial TRAK adaptors activate the dynein-dynactin complex, enhance the motility of kinesin, and can scaffold both motors to control bidirectional transport.
- John T. Canty
- , Andrew Hensley
- & Ahmet Yildiz
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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 AccessVariable microtubule architecture in the malaria parasite
Microtubules are a ubiquitous eukaryotic cytoskeletal element typically consisting of 13 protofilaments arranged in a hollow cylinder. Using CryoEM and subvolume averaging, Ferreira and Pražák et al. show that Plasmodium does not adhere to a single microtubule structure. Instead, the cytoskeleton changes substantially to produce a unique, fit for purpose structure and organisation at each stage of its life cycle.
- Josie L. Ferreira
- , Vojtěch Pražák
- & Kay Grünewald
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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 AccessSalmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection
Vimentin is an intermediate filament protein responsible for maintaining cell shape. Here, the authors characterise the role of the Salmonella effector SopB on the vimentin network and its contribution to infection.
- Shuangshuang Zhao
- , Qiuping Xu
- & Yaming Jiu
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Article
| Open AccessMicrotubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG
The molecular mechanisms underpinning the organization of microtubule arrays remain unclear. Here the authors show that in human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi through a mechanism that involves transient interaction with the microtubule nucleator γTuRC.
- Aamir Ali
- , Chithran Vineethakumari
- & Jens Lüders
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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 AccessAge-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity
Matrix stiffening is a quintessential feature of aged tissues. Authors show that an aged (stiff) matrix epigenetically represses the gene encoding the longevity factor, α-Klotho, resulting in chondrocyte dysfunction, a leading cause of osteoarthritis.
- Hirotaka Iijima
- , Gabrielle Gilmer
- & Fabrisia Ambrosio
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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 AccessRegulation of bone homeostasis by MERTK and TYRO3
The TAM family of receptor tyrosine kinases exerts pleiotropic functions in health and disease. Here, the authors show that TAM receptors control osteoblastic bone formation and identified MERTK as a novel target for bone anabolic therapy and mitigation of bone metastasis including its associated osteolytic bone disease
- Janik Engelmann
- , Jennifer Zarrer
- & Sonja Loges
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Article
| Open AccessKinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
Mitotic spindle assembly is not fully understood. This work reveals that kinetochores drive the coarsening of a uniform microtubule array into bundles, which promote spindle formation and chromosome segregation fidelity.
- Jurica Matković
- , Subhadip Ghosh
- & Iva M. Tolić
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Article
| Open AccessFeedback between mechanosensitive signaling and active forces governs endothelial junction integrity
Gap formation in the vasculature underpins immune and tumour cell infiltration. Here the authors propose a chemo-mechanical model to analyse how feedback between mechanosensitive signalling, active cellular forces and adhesion governs the breakdown, recovery, and integrity of endothelial junctions.
- Eoin McEvoy
- , Tal Sneh
- & Vivek B. Shenoy
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Article
| Open AccessBiasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration
Myoblast fusion is essential for development of multinucleated myofibers. Here, the authors show that ablation of Elmo 1 and Elmo2 impairs myoblast fusion in mice, and that expression of an open conformation of Elmo2 promotes muscle regeneration and improves the phenotype of Dysferlin-null dystrophic mice.
- Viviane Tran
- , Sarah Nahlé
- & Jean-François Côté
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Article
| Open AccessPatterned mechanical feedback establishes a global myosin gradient
How does DNA encode shape? Here, via in toto light sheet microscopy and optogenetic control of cellular forces, the authors show that spatially patterned mechanical feedback loops establish the cytoskeletal patterns driving axis elongation tissue flow in Drosophila.
- Hannah J. Gustafson
- , Nikolas Claussen
- & Sebastian J. Streichan
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Article
| Open AccessCytoskeletal components can turn wall-less spherical bacteria into kinking helices
The cell wall and cytoplasmic MreB polymers are important for bacterial cell shape. However, Spiroplasma cells lack a cell wall and still display a helical shape and kink-based motility, which is thought to rely on five MreB isoforms and a fibril protein. Here, Lartigue et al. show that heterologous expression of a single Spiroplasma MreB isoform confers helical shape and kinking ability to Mycoplasma cells, which are naturally spherical and non-motile.
- Carole Lartigue
- , Bastien Lambert
- & Laure Béven
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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 AccessCaldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments
In this study the authors report that Caldesmon controls force-balance and architecture of stress fibers through dynamic cross-linking of actin and myosin filaments. Caldesmon depletion led to consequent problems in cell morphogenesis, motility and mechanosensing.
- Shrikant B. Kokate
- , Katarzyna Ciuba
- & Pekka Lappalainen
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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