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| 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
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Article
| Open AccessCofilactin filaments regulate filopodial structure and dynamics in neuronal growth cones
In this manuscript the authors show that Filopodia switch between bundles of fascin-crosslinked actin and cofilin-decorated filaments, which exclude fascin binding due to altered structure and packing, as well as affect filopodial searching dynamics.
- Ryan K. Hylton
- , Jessica E. Heebner
- & Matthew T. Swulius
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Article
| Open AccessSimultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury
A common cellular manifestation for diverse kidney diseases is dysregulated actin cytoskeleton in distinct cell types that include glomerular podocytes and tubular epithelial cells. Here, authors pharmacologically activate dynamin and this results in polymerization and crosslinking of actin filaments to establish the structural integrity of these cells, thus ameliorating disease phenotypes.
- Kamalika Mukherjee
- , Changkyu Gu
- & Sanja Sever
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Article
| Open AccessCytonemes coordinate asymmetric signaling and organization in the Drosophila muscle progenitor niche
Asymmetric signaling and organization in the stem cell niche determine cell fates. Here the authors show that polarized contact-dependent signaling through specialized cytonemes forms the basis of niche-specific asymmetric signaling and stem cell organization.
- Akshay Patel
- , Yicong Wu
- & Sougata Roy
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Article
| Open AccessASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis
The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.
- Christophe Royer
- , Elizabeth Sandham
- & Shankar Srinivas
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Article
| Open AccessMatrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin
Epithelial cells have the ability to competitively remove potentially cancerous cells from the tissue. Here the authors discover that pathological stiffening of extracellular matrix leads to the loss of this basic epithelial defence against cancer.
- Shilpa P. Pothapragada
- , Praver Gupta
- & Tamal Das
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Article
| Open AccessExtent of myosin penetration within the actin cortex regulates cell surface mechanics
Cellular deformations are largely driven by contractile forces generated by myosin motors in the submembraneous actin cortex. Here we show that these forces are controlled not simply by cortical myosin levels, but rather by myosins spatial arrangement, specifically the extent of their overlap with cortical actin.
- Binh An Truong Quang
- , Ruby Peters
- & Ewa K. Paluch
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Article
| Open AccessPlexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion
Biomechanical mechanisms orchestrating stem cell dynamics in development remain unclear. Here the authors show that guidance receptor Plexin-B2 organizes actomyosin contractility, cytoskeletal tension and adhesion during multicellular development of human embryonic stem cells and neuroprogenitor cells.
- Chrystian Junqueira Alves
- , Rafael Dariolli
- & Roland H. Friedel
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Article
| Open AccessNance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.
- Ah-Lai Law
- , Shamsinar Jalal
- & Matthias Krause
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Article
| Open AccessProfilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.
- Elena E. Grintsevich
- , Giasuddin Ahmed
- & Jonathan R. Terman
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Article
| Open AccessAnillin propels myosin-independent constriction of actin rings
Cytokinetic ring constriction during cell division requires actin but curiously is independent of myosin in many organisms. Here, the authors show that anillin, a protein enriched in the contractile ring, is a non-motor actin crosslinker that generates contractile force in lieu of a molecular motor.
- Ondřej Kučera
- , Valerie Siahaan
- & Zdenek Lansky
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Article
| Open AccessCorrelative 3D microscopy of single cells using super-resolution and scanning ion-conductance microscopy
Methods for imaging the 3D cell surface often require physical interaction. Here the authors report the combination of scanning ion conductance microscopy (SICM) and live-cell super-resolution optical fluctuation imaging (SOFI) for the non-invasive topographical imaging of soft biological samples.
- Vytautas Navikas
- , Samuel M. Leitao
- & Georg E. Fantner
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Article
| Open AccessKRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals
Calcium signals initiated by IP3 receptors in ER membranes regulate most cellular activities. Here, the authors show that KRas-induced actininteracting protein (KRAP) tethers a small subset of IP3 receptors to actin and licenses them to evoke cytosolic calcium signals.
- Nagendra Babu Thillaiappan
- , Holly A. Smith
- & Colin W. Taylor
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Article
| Open AccessThe force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening
Cells sense mechanical forces from their environment, but the precise mechanical variable sensed by cells is unclear. Here, the authors show that cells can sense the rate of force application, known as the loading rate, with effects on YAP nuclear localization and cytoskeletal stiffness remodelling.
- Ion Andreu
- , Bryan Falcones
- & Pere Roca-Cusachs
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Article
| Open AccessMolecular-scale visualization of sarcomere contraction within native cardiomyocytes
Sarcomeres, the building blocks of striated muscles, comprise ordered actomyosin arrays involved in force production. Here, the authors visualize sarcomere organization in neonatal cardiomyocytes with in situ cryo-electron tomography, revealing a reduced order of the thin filaments, their sliding and functional states enabling contraction.
- Laura Burbaum
- , Jonathan Schneider
- & Marion Jasnin
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Article
| Open AccessA release-and-capture mechanism generates an essential non-centrosomal microtubule array during tube budding
Non-centrosomal microtubules provide essential functions in many cells, but the mechanisms of their formation are poorly understood. Here, the authors show that during tube formation of the Drosophila salivary glands, microtubules are released from a single active centrosome via katanin, triggering recruitment of Patronin, and leading to formation of a non-centrosomal network key to the tube invagination process.
- Ghislain Gillard
- , Gemma Girdler
- & Katja Röper
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Article
| Open AccessXanthomonas effector XopR hijacks host actin cytoskeleton via complex coacervation
Bacterial pathogens can subvert host cell processes through secreted proteins but the precise mechanisms and repertoire of proteins remains unclear. Here the authors report that a bacterial effector protein of Xanthomonas campestris, XopR, undergoes liquid-liquid phase separation to hijack the host cell actin cytoskeleton.
- He Sun
- , Xinlu Zhu
- & Yansong Miao
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Article
| Open AccessNEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA
Ciliogenesis is a tightly regulated process, although the role of selective autophagy is unclear. Here, the authors show NIMA-related kinase 9 controls actin network stabilization and subsequently ciliogenesis by targeting myosin MYH9 for autophagic degradation via GABARAP interaction.
- Yasuhiro Yamamoto
- , Haruka Chino
- & Noboru Mizushima
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Article
| Open AccessRHOA signaling defects result in impaired axon guidance in iPSC-derived neurons from patients with tuberous sclerosis complex
Patients with Tuberous Sclerosis Complex (TSC) show aberrant wiring of neuronal connections. Here, the authors generate iPSC-derived neurons from patients with TSC. TSC2 +/− neurons show impaired mTOR-independent RhoA signaling-mediated axon guidance.
- Timothy S. Catlett
- , Massimo M. Onesto
- & Timothy M. Gómez
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Article
| Open AccessInhibition of polar actin assembly by astral microtubules is required for cytokinesis
During cell division, the actin cytoskeletal network at both the equatorial contractile ring and cell cortex are known to play a role, but the regulation of γ-actin during cytokinesis is less well understood. Here, the authors show that recruitment of β-actin to the contractile ring and loss of γ-actin from the cell poles is required for completion of cell division.
- Anan Chen
- , Luisa Ulloa Severino
- & Andrew Wilde
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Article
| Open AccessReconstitution of contractile actomyosin rings in vesicles
Cytoskeletal networks support and direct cell shape and guide intercellular transport, but relatively little is understood about the self-organization of cytoskeletal components on the scale of an entire cell. Here, authors use an in vitro system and observe the assembly of different types of actin networks and the condensation of membrane-bound actin into single rings.
- Thomas Litschel
- , Charlotte F. Kelley
- & Petra Schwille
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Article
| Open AccessDrebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking
Reactive astrocytes control tissue damage following traumatic brain injury. Here the authors show that Drebrin (DBN) regulates scar formation and astrocyte reactivity in mice. Astrocytic DBN plays its neuroprotective role through the mediation of membrane trafficking.
- Juliane Schiweck
- , Kai Murk
- & Britta J. Eickholt
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Article
| Open AccessEpidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation
Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.
- Laleh Abbassi
- , Stephany El-Hayek
- & Hugh J. Clarke
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Article
| Open AccessA functional family of fluorescent nucleotide analogues to investigate actin dynamics and energetics
Actin polymerization provides force for vital processes of the eukaryotic cell, but our understanding of actin dynamics and energetics remains limited due to the lack of high-quality probes. Here authors identify a family of highly sensitive fluorescent nucleotide analogues which bind to actin and provide energy to power actin-based processes.
- Jessica Colombo
- , Adrien Antkowiak
- & Alphée Michelot
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Article
| Open AccessSTIM-Orai1 signaling regulates fluidity of cytoplasm during membrane blebbing
The cytoplasm in mammalian cells is considered homogeneous. Here authors report that the cytoplasmic fluidity is regulated in the blebbing cells, which is regulated by calcium concentration in the expanding blebs and involves the STIM-Orai1 pathway.
- Kana Aoki
- , Shota Harada
- & Junichi Ikenouchi
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Article
| Open AccessCryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction
The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Here, authors report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging.
- Florian Fäßler
- , Georgi Dimchev
- & Florian K. M. Schur
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Article
| Open AccessBiased localization of actin binding proteins by actin filament conformation
The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology. Here, the authors use a combination of live cell imaging and in vitro single molecule binding measurements to show that tandem calponin homology domains (CH1–CH2) are sensitive to actin filament conformation, biasing their subcellular localization.
- Andrew R. Harris
- , Pamela Jreij
- & Daniel A. Fletcher
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Article
| Open AccessVascular surveillance by haptotactic blood platelets in inflammation and infection
Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets
- Leo Nicolai
- , Karin Schiefelbein
- & Florian Gaertner
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Article
| Open AccessMarcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size
During lumen formation in blood vessels, endothelial cells become exposed to hemodynamic forces that induce membrane blebbing and changes in cell shape. Here, the authors show endothelial cells develop an actin-based protective mechanism in the cell cortex that prevents excessive blebbing to control cell shape and vessel diameter.
- Igor Kondrychyn
- , Douglas J. Kelly
- & Li-Kun Phng
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Article
| Open AccessE-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow
The arrival of migratory cells at their targets relies on following precise routes within tissues. Here the authors demonstrate that the cell adhesion molecule E-cadherin can control the path of cell migration by confining the site where bleb-type protrusions form within the cell front.
- Cecilia Grimaldi
- , Isabel Schumacher
- & Erez Raz
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Article
| Open AccessSynaptic vesicle traffic is supported by transient actin filaments and regulated by PKA and NO
Transport of membrane proteins within the cell is thought to mainly rely on microtubule-based transport, but the role of microtubules in neuronal cell recycling of synaptic vesicles is unclear. Here, the authors show that axonal movement of recycling vesicles may be driven not by microtubules but primarily by actin polymerization.
- Nicolas Chenouard
- , Feng Xuan
- & Richard W. Tsien
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Article
| Open AccessComplementary mesoscale dynamics of spectrin and acto-myosin shape membrane territories during mechanoresponse
The cell cortex that supports the plasma membrane contains spectrin, a protein that interacts with the acto-myosin cytoskeleton. Here, the authors analyze spectrin behavior during cellular mechanoresponse and membrane trafficking, and observe spectrin regulation by myosin-driven contractility.
- Andrea Ghisleni
- , Camilla Galli
- & Nils C. Gauthier
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Article
| Open AccessRab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins
Melanosomes traffic along F-actin in melanocytes. Here, the authors show that Rab27a coordinates SPIRE/FMN actin assembly and MyoVa motor proteins to generate a cell-wide actin/myosin network that links melanosomes and allows the collective activity of these force generators to drive their traffic.
- Noura Alzahofi
- , Tobias Welz
- & Alistair N. Hume
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Article
| Open AccessTug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement
Symmetric or asymmetric positioning of intracellular structures such as the nucleus and mitotic spindle steers various biological processes. Here authors use an in vitro model and show that a tug-of-war between centripetal actomyosin waves and percolation of bulk actomyosin network direct the positioning.
- Ryota Sakamoto
- , Masatoshi Tanabe
- & Makito Miyazaki
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Article
| Open AccessA Cdc42-mediated supracellular network drives polarized forces and Drosophila egg chamber extension
During development, organs undergo large scale forces driven by the cytoskeleton but the precise molecular regulation of cytoskeletal networks remains unclear. Here, the authors report a Cdc42-dependent supracellular cytoskeletal network integrates local actomyosin contraction at tissue scale and drives global tissue elongation.
- Anna Popkova
- , Orrin J. Stone
- & Xiaobo Wang
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Article
| Open AccessArtificially decreasing cortical tension generates aneuploidy in mouse oocytes
The developmental potential of human and murine oocytes is predicted by their mechanical properties. Here the authors show that artificial reduction of cortex tension produces aneuploid mouse oocytes and speculate that this may contribute to the high aneuploidy rate typical of female meiosis.
- Isma Bennabi
- , Flora Crozet
- & Marie-Emilie Terret
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Article
| Open AccessOptogenetic regulation of endogenous proteins
Optogenetic approaches to control protein-protein interactions usually require overexpression of the target proteins. Here the authors integrate intrabodies into near-infrared- and blue-light activatable optogenetic tools to control endogenous proteins in mammalian cells.
- Taras A. Redchuk
- , Maksim M. Karasev
- & Vladislav V. Verkhusha
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Article
| Open AccessDynamic organelle distribution initiates actin-based spindle migration in mouse oocytes
Mammalian oocytes divide asymmetrically during meiotic maturation. Here, the authors show that spindle movement away from oocyte center depends on actin filaments nucleated from the spindle periphery pushing against surrounding mitochondria, which polarizes spontaneously to produce directional spindle motion.
- Xing Duan
- , Yizeng Li
- & Rong Li
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Article
| Open AccessUltrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
The ultrastructural details of the periodic scaffold of actin rings under the plasma membrane of axons remain unknown. Here, the authors combine platinum-replica electron and optical super-resolution microscopy and resolve actin rings as braids made of two long, intertwined actin filaments connected by a dense mesh of aligned spectrins.
- Stéphane Vassilopoulos
- , Solène Gibaud
- & Christophe Leterrier
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Article
| Open AccessSynergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude
Cellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize over minutes. Here the authors show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends 330-fold faster than spontaneous depolymerization.
- Shashank Shekhar
- , Johnson Chung
- & Bruce L. Goode
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Article
| Open AccessGPCR-induced calcium transients trigger nuclear actin assembly for chromatin dynamics
The extracellular cues regulating filamentous actin formation in somatic cell nuclei are unclear. Here, the authors show that activated GPCR signalling initiates transient accumulation of nuclear F-actin/formation in nuclear actin filaments, driven by calcium and requiring the nucleator Formin INF2.
- Ying Wang
- , Alice Sherrard
- & Robert Grosse
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Article
| Open AccessModular actin nano-architecture enables podosome protrusion and mechanosensing
Podosomes are actin-based protrusions used by cells for invasion and local degradation but the structure underlying their protrusiveness and mechanosensitivity is unclear. Here, the authors report that podosomes have a modular actin nano-architecture whose organization differs on stiff or soft substrates.
- Koen van den Dries
- , Leila Nahidiazar
- & Alessandra Cambi
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Article
| Open AccessActin-microtubule interplay coordinates spindle assembly in human oocytes
Actin and microtubules contribute to successful oocyte maturation, but if and how these two networks communicate in human oocytes is unclear. Here the authors show that actin-microtubule interactions are essential for correct segregation of human nuclear genomic content.
- Johannes Roeles
- & Georgios Tsiavaliaris
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Article
| Open AccessVimentin filaments interact with the actin cortex in mitosis allowing normal cell division
The intermediate filament vimentin reorganizes during mitosis, but its molecular regulation and impact on the cell during cell division is unclear. Here, the authors show that vimentin filaments redistribute to the cell cortex during mitosis intertwining with and affecting actin organization.
- Sofia Duarte
- , Álvaro Viedma-Poyatos
- & Dolores Pérez-Sala
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Article
| Open AccessA highly dynamic F-actin network regulates transport and recycling of micronemes in Toxoplasma gondii vacuoles
Replication of Toxoplasma gondii requires replication and distribution of essential organelles such as micronemes. Here, Periz et al. show that micronemes are recycled from the mother to the forming daughter cells using a highly dynamic F-actin network that supports multidirectional vesicle transport.
- Javier Periz
- , Mario Del Rosario
- & Markus Meissner
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Article
| Open AccessWHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes
After autophagic cargo degradation, autolysosomes undergo a reformation process to recycle lysosomal membrane components. Here, Dai et al. demonstrate that the actin nucleation promoting factor WHAMM is required for autolysosome reformation by providing an actin scaffold to drive tubulation.
- Anbang Dai
- , Li Yu
- & Hong-Wei Wang
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Article
| Open AccessMyosin IIA and formin dependent mechanosensitivity of filopodia adhesion
Fiolopodia are involved in cell migration and their attachment to the ECM is mediated by integrin receptors. Here the authors show that myosin X induced filipodia adhesion to fibronectin requires activity of myosin IIA at the filopodium base and formin at the tip to support force transmission through the actin core.
- N. O. Alieva
- , A. K. Efremov
- & A. D. Bershadsky