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| Open AccessEvidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.
- Cédric Castrogiovanni
- , Alessio V. Inchingolo
- & Patrick Meraldi
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Article
| Open AccessSynaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
How pancreatic islets of Langerhans are built during development is incompletely understood. Here the authors find that Synaptotagmin-13 mediates remodeling of cell-matrix adhesion to regulate endocrine cell egression and islet morphogenesis.
- Mostafa Bakhti
- , Aimée Bastidas-Ponce
- & Heiko Lickert
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Article
| Open AccessActin nano-architecture of phagocytic podosomes
Podosomes are actin structures important in multiple cell functions. Here, the authors use iPALM microscopy to reveal an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from it.
- J. Cody Herron
- , Shiqiong Hu
- & Klaus M. Hahn
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Article
| Open AccessThe architecture of kinesin-3 KLP-6 reveals a multilevel-lockdown mechanism for autoinhibition
Autoinhibition ensures the proper spatiotemporal control of the kinesin-3 motor activity. Here, the authors present the full-length structure of kinesin-3 KLP-6 in an autoinhibited state and observe that all the internal domains entwine around the motor domain via a multilevel-lockdown mechanism.
- Wenjuan Wang
- , Jinqi Ren
- & Wei Feng
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Article
| Open AccessMechanism of threonine ADP-ribosylation of F-actin by a Tc toxin
Entomopathogenic bacteria used for pest control secrete potent Tc toxins. Here, the authors combine biochemistry, solution and solid-state NMR spectroscopy and cryo-EM to show in atomic detail how the toxin disrupts the host cell cytoskeleton and kills the target cell.
- Alexander Belyy
- , Florian Lindemann
- & Stefan Raunser
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Article
| Open AccessNestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing
The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
- Senyu Yao
- , Xiaoyue Wei
- & Jiancheng Wang
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Article
| Open AccessCiliary transition zone proteins coordinate ciliary protein composition and ectosome shedding
Cilia project from cells to serve sensory functions, and ciliary disruption can result in multiple disorders known as ciliopathies. Here the authors show that the ciliopathy gene TCTN1 functions to regulate the ciliary transition zone and ectosome formation.
- Liang Wang
- , Xin Wen
- & Muqing Cao
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| Open AccessElasticity of podosome actin networks produces nanonewton protrusive forces
Actin filaments generate force in diverse contexts, although how they can produce nanonewtons of force is unclear. Here, the authors apply cryo-electron tomography, quantitative analysis, and modelling to reveal the podosome core is a dense, spring-loaded, actin network storing elastic energy.
- Marion Jasnin
- , Jordan Hervy
- & Renaud Poincloux
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Article
| Open AccessThe force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail
Tubulin, the building blocks of microtubules, can be removed from the microtubule wall by mechanical forces. Using single-molecule methods, the authors show that tubulin partially unfolds prior to its removal and determined the tubulin-extraction force.
- Yin-Wei Kuo
- , Mohammed Mahamdeh
- & Jonathon Howard
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Article
| Open AccessMicrotubule disassembly by caspases is an important rate-limiting step of cell extrusion
Using the Drosophila pupal notum, the authors demonstrate that the disassembly of microtubules by effector caspases initiate cell extrusion independently of actomyosin regulation, thus providing insights into how caspases orchestrate dying epithelial cell expulsion.
- Alexis Villars
- , Alexis Matamoro-Vidal
- & Romain Levayer
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Article
| Open AccessA glycine-rich PE_PGRS protein governs mycobacterial actin-based motility
Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. Here, Hill & Welch identify an M. marinum surface protein that binds to and activates the host protein NWASP to stimulate actin polymerization and drive bacterial actin-based motility.
- Norbert S. Hill
- & Matthew D. Welch
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Article
| Open AccessBranched actin networks are organized for asymmetric force production during clathrin-mediated endocytosis in mammalian cells
Drubin et al. use three different advanced imaging approaches to show that actin assembles preferentially at stalled clathrin-mediated endocytosis sites, where the actin pulls vesicles into the cell asymmetrically, as a bottle opener pulls off a cap.
- Meiyan Jin
- , Cyna Shirazinejad
- & David G. Drubin
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Article
| Open AccessInhibition of negative feedback for persistent epithelial cell–cell junction contraction by p21-activated kinase 3
Actin and myosin operate at cell–cell junctions during junctional shortening. Here the authors show that prolonged actomyosin contractility can compromise junctional shortening, and that Pak3 is required for attenuation of abnormal active protrusive structure and thus keeps junction contraction, appropriate E-cadherin distribution, and junction shortening in Drosophila.
- Hiroyuki Uechi
- , Kazuki Fukushima
- & Erina Kuranaga
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Article
| Open AccessStructural basis of rapid actin dynamics in the evolutionarily divergent Leishmania parasite
The authors report here the structure-function analysis of highly divergent actin from Leishmania parasite. The study reveals remarkably rapid dynamics of parasite actin as well as the underlying molecular basis, thus providing insight into evolution of the actin cytoskeleton.
- Tommi Kotila
- , Hugo Wioland
- & Pekka Lappalainen
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Article
| Open AccessProteomic and functional analyses of the periodic membrane skeleton in neurons
In neurons the membrane-associated periodic skeleton (MPS) consists of actin, spectrin, and associated molecules. Here the authors use proteomic analysis and super-resolution imaging to provide insight into the molecular composition and organization of the MPS, and its functions in axon-diameter regulation and neurite-neurite interactions.
- Ruobo Zhou
- , Boran Han
- & Xiaowei Zhuang
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Article
| Open AccessNovel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development
The Dlgap protein family members are known for their role in synapses. Here the authors reveal important involvement in earlier steps of brain development, identifying DLGAP4 mutations in patients with cortical malformations, and also demonstrating a role in progenitors and migrating neurons.
- Delfina M. Romero
- , Karine Poirier
- & Fiona Francis
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Article
| Open AccessIdentification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast
Actin cables affect lifespan by supporting movement and inheritance of fitter mitochondria to daughter cells in yeast. Here the authors show that branched-chain amino acid (BCAA) levels affect actin cable stability and a role for YKL075C/AAN1 in control of BCAA metabolism and actin cable stability and function.
- Cierra N. Sing
- , Enrique J. Garcia
- & Liza A. Pon
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Article
| Open AccessMechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS
The structure of the mitochondrial inner membrane, or cristae, is important for functional oxidative phosphorylation and energy production. Here, the authors show that loss of myosin 19 impairs cristae structure as well as energy production, connecting motor activity to membrane potential.
- Peng Shi
- , Xiaoyu Ren
- & Congying Wu
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Article
| Open AccessRegulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms
Recent work has shown that mammalian muscle cells are comprised of multiple branching sarcomeres, though how this connectivity is regulated has remained unknown. Here the authors show three different mechanisms which regulate connectivity of the muscle contractile apparatus.
- Peter T. Ajayi
- , Prasanna Katti
- & Brian Glancy
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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 AccessMicroridge-like structures anchor motile cilia
Motile cilia beat in a defined direction to orchestrate developmental programs, but also to execute janitorial tasks such as clearing airways. Here they show that motile cilia of the Xenopus epidermis are anchored to microridge-like membrane protrusions to maintain their directionality.
- Takayuki Yasunaga
- , Johannes Wiegel
- & Gerd Walz
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Article
| Open AccessRUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin
Organellar transport is carefully regulated, and endolysosome localized ARL8 is important for kinesin recruitment and anterograde movement. Here, the authors show that RUFY3 and RUFY4 promote retrograde transport of endolysosomes by mediating interaction of ARL8 with dynein-dynactin.
- Tal Keren-Kaplan
- , Amra Sarić
- & Juan S. Bonifacino
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Article
| Open AccessPrimary cilia on muscle stem cells are critical to maintain regenerative capacity and are lost during aging
Repair of muscle damage requires muscle stem cells, which lose regenerative capacity with aging. Here, the authors show that a sensory organelle, the primary cilium, is critical for muscle stem cell proliferation during regeneration and lost with aging.
- Adelaida R. Palla
- , Keren I. Hilgendorf
- & Helen M. Blau
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Article
| Open AccessCEP128 is involved in spermatogenesis in humans and mice
CEP128 is a centrosomal protein important for the organization of centriolar microtubules. Here, the authors show that a CEP128 variant observed in human male siblings causes reduced sperm counts and morphologically abnormal sperm when modeled in mice, suggesting a role for CEP128 in male fertility.
- Xueguang Zhang
- , Lingbo Wang
- & Ying Shen
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Article
| Open AccessβIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling
Defective angiogenesis remains a high source of morbidity in multiple disorders. Here they show that βIV-spectrin, a membrane-associated cytoskeletal protein, is essential for regulation of endothelial tip cell populations and VEGF signaling during sprouting angiogenesis.
- Eun-A Kwak
- , Christopher C. Pan
- & Nam Y. Lee
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Article
| Open AccessLoss of the Bardet-Biedl protein Bbs1 alters photoreceptor outer segment protein and lipid composition
Primary cilia are key sensory organelles whose dysfunction leads to ciliopathy disorders such as Bardet-Biedl syndrome (BBS). Here they identify a role for Bbs1 in lipid homeostasis of photoreceptor outer segments in zebrafish, which may contribute to vision loss in patients with Bardet-Biedl syndrome.
- Markus Masek
- , Christelle Etard
- & Ruxandra Bachmann-Gagescu
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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 AccessRecruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions
The kinetochores contain multiple protein interaction networks. Takenoshita et al. analyzed the complicated networks using the genetic method and revealed that two copies of Ndc80 complexes on CENP-T are sufficient for kinetochore functions.
- Yusuke Takenoshita
- , Masatoshi Hara
- & Tatsuo Fukagawa
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Article
| Open AccessSpatiotemporal expression of regulatory kinases directs the transition from mitosis to cellular morphogenesis in Drosophila
The mechanisms regulating mitosis and differentiation during development are thought to be distinct. Here they show that in Drosophila the mitotic kinase Polo regulates cellular morphogenesis after cell cycle exit.
- Shuo Yang
- , Jennifer McAdow
- & Aaron N. Johnson
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Article
| Open AccessModular assembly of the principal microtubule nucleator γ-TuRC
The human microtubule nucleator γ-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular γ-TuRC assembly and show a functional role of actin in microtubule nucleation.
- Martin Würtz
- , Erik Zupa
- & Stefan Pfeffer
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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 AccessNuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation
Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.
- Mengjie Sun
- , Mingkang Jia
- & Chuanmao Zhang
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Article
| Open AccessCilia locally synthesize proteins to sustain their ultrastructure and functions
Cilia are microtubule-based organelles containing proteins transported from the cell body. Here, the authors show that the multicilia of mouse ependymal cells contain ribosomal components, tubulin mRNA,18 S rRNA and nascent tubulin peptides, suggesting local translation in the ciliary compartment.
- Kai Hao
- , Yawen Chen
- & Xueliang Zhu
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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 AccessAgrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing
Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.
- Sayan Chakraborty
- , Divyaleka Sampath
- & Wanjin Hong
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Article
| Open AccessMicrotubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle
It is increasingly recognised that the spatial localisation of RNA is important for proper cellular function. Here, the authors investigate RNA localisation in skeletal muscle and develop methods to show that global active transport of RNA is required to maintain dispersion of gene products in the large muscle syncytium.
- Lance T. Denes
- , Chase P. Kelley
- & Eric T. Wang
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Article
| Open AccessSub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold
The γ-tubulin ring complex (γTuRC) nucleates microtubules at the centrosome, but how this function is related to γTuRC subcentrosomal distribution is unclear. Here the authors show that γTuRC in the centriole lumen has a nucleation-independent role in centriole integrity and cilium assembly.
- Nina Schweizer
- , Laurence Haren
- & Jens Lüders
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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 AccessWdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules
Ciliary beating is mediated by the axonemal central pair microtubules, though how these non-centrosomal microtubules form is poorly understood. Here the authors show that a trio of proteins act cooperatively to initiate central microtubule formation in mammals.
- Hao Liu
- , Jianqun Zheng
- & Xiumin Yan
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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 AccessPERM1 interacts with the MICOS-MIB complex to connect the mitochondria and sarcolemma via ankyrin B
Mitochondria in skeletal muscle have distinct localization and properties through unclear mechanisms. Here, the authors use complexome profiling and immunoprecipitations to identify PERM1 as a MICOS-MIB complex interactor that also binds ankyrin B, suggesting PERM1 directs the mitochondria to the membrane.
- Theresa Bock
- , Clara Türk
- & Marcus Krüger
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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