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| Open AccessHow Leiomodin and Tropomodulin use a common fold for different actin assembly functions
Leiomodins and Tropomodulins are related, but have different functions; actin filament nucleation and pointed end capping, respectively. Here, the authors use structural, biochemical and cellular approaches to show how these different activities have evolved based on a common protein fold.
- Malgorzata Boczkowska
- , Grzegorz Rebowski
- & Roberto Dominguez
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Article
| Open AccessDirect observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules
Cytoplasmic dynein is a dimeric protein that steps processively along microtubules. Here Imaiet al. present cryo-electron microscopy images of stepping D. discoideumdynein, revealing diverse microtubule-bound configurations including a hinge-dependent, motors side-by-side arrangement.
- Hiroshi Imai
- , Tomohiro Shima
- & Stan A. Burgess
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Article
| Open AccessPlk1 relieves centriole block to reduplication by promoting daughter centriole maturation
The orthogonal orientation between centrioles is thought to prevent their reduplication. Shukla et al.show that Polo-like kinase 1-dependent daughter centriole maturation, reflected in increasing inter-centriolar distance, allows centriole reduplication prior to loss of orthogonal orientation.
- Anil Shukla
- , Dong Kong
- & Jadranka Loncarek
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| Open AccessNek2 activation of Kif24 ensures cilium disassembly during the cell cycle
Most differentiated mammalian cells assemble a primary cilium, which serves as a cellular ‘antenna’ for sensing and responding to the extracellular environment. Here the authors show that Nek2-mediated phosphorylation of Kif24 further promotes the loss of primary cilia, triggered by Aurora A and HDAC6 on cell cycle re-entry.
- Sehyun Kim
- , Kwanwoo Lee
- & Brian David Dynlacht
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| Open AccessFormation of helical membrane tubes around microtubules by single-headed kinesin KIF1A
The kinesin-3 motor KIF1A is inefficient in its single-headed form but recent studies have predicted that force transmission is enabled when motors work in teams. Here Oriola et al.show that singleheaded KIF1A motors can pull tubes from lipid vesicles, and form left-handed helices around microtubules by generating lateral forces.
- David Oriola
- , Sophie Roth
- & Jaume Casademunt
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Article
| Open AccessResolving bundled microtubules using anti-tubulin nanobodies
Super-resolution imaging of microtubules requires labels that increase their apparent diameter, making it difficult to resolve individual microtubules within a bundle. Here, the authors develop single-chain antibody fragments against tubulin that enable closely spaced individual microtubules to be distinguished in cells.
- Marina Mikhaylova
- , Bas M. C. Cloin
- & Lukas C Kapitein
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| Open AccessAn epigenetic regulator emerges as microtubule minus-end binding and stabilizing factor in mitosis
The heptameric KAT8-associated nonspecific lethal complex consists of highly conserved chromatin modifier proteins. Here, the authors show a role for the members of the complex in regulating microtubule assembly during mitosis.
- Sylvain Meunier
- , Maria Shvedunova
- & Asifa Akhtar
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| Open AccessMto2 multisite phosphorylation inactivates non-spindle microtubule nucleation complexes during mitosis
In S. pombe, cytoplasmic microtubule nucleation, which depends on the Mto1/2 complex, ceases during mitosis. Here, Borek et al., show that multisite phosphorylation of Mto1/2 during mitosis disassembles the Mto1/2 complex and prevents microtubule nucleation activity.
- Weronika E. Borek
- , Lynda M. Groocock
- & Kenneth E. Sawin
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Article
| Open AccessHarmonic force spectroscopy measures load-dependent kinetics of individual human β-cardiac myosin molecules
Single molecule methods for measuring load dependence are fundamental for molecular motor research. Here, Sung et al. introduce harmonic force spectroscopy, a method that randomly applies varying loads at high frequency, allowing the determination of load dependent parameters of human β-cardiac myosin at physiological ATP concentration.
- Jongmin Sung
- , Suman Nag
- & James A. Spudich
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| Open AccessActin nucleation by WH2 domains at the autophagosome
Autophagy is a catabolic process whereby cellular components are degraded by the autophagosome, but the role of the actin cytoskeleton is not clear. Here Coutts and La Thangue show that the actin nucleator JMY is recruited to the autophagosome via binding LC3, and promotes actin nucleation that is required for autophagosome maturation.
- Amanda S. Coutts
- & Nicholas B. La Thangue
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Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process
Damaged DNA is often targeted to nuclear pore complexes for repair. Here, the authors show that kinesin-14 mediates this process ensuring error-prone repair, while perinuclear telomere attachment licenses damaged telomeric loci for this repair and kinesin-14 blocks senescence in the absence of telomerase.
- Daniel K.C. Chung
- , Janet N.Y. Chan
- & Karim Mekhail
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HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity
Retracted neurites and disorganized actin filaments are major components of senile plaques and neurofibrillary tangles—hallmarks of Alzheimer's disease. Here the authors show that soluble ß-amyloid impairs action potential firing by disrupting actin and microtubule filaments through the inhibition of HDAC6 and activation of RhoA.
- Hanako Tsushima
- , Marco Emanuele
- & Evelina Chieregatti
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| Open AccessAn actin-dependent spindle position checkpoint ensures the asymmetric division in mouse oocytes
In mammalian oocytes, the meiotic spindle is assembled close to the centre of the cell and relocates to the cell periphery prior to chromosome segregation. Here Metchat et al. show that anaphase is delayed until the spindle is positioned close to the cell cortex, providing evidence for a spindle position checkpoint.
- Aïcha Metchat
- , Manuel Eguren
- & Jan Ellenberg
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CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
CEP63 is a centrosomal protein that is mutated in the microcephaly disease Seckel syndrome. Here the authors disrupt Cep63 in the mouse and find that neural progenitor cells undergo p53-dependent cell death, and uncover a role for CEP63 in ensuring correct meiotic recombination in male gametes.
- Marko Marjanović
- , Carlos Sánchez-Huertas
- & Travis H. Stracker
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| Open AccessA three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes
Mitotic spindles assemble from two centrosomes, but oocytes lack centrosomes so how their spindles assemble is unclear. Here Clift and Schuh show that multiple acentriolar microtubule-organizing centres fragment in a three-step process to facilitate bipolar spindle assembly in mouse oocytes.
- Dean Clift
- & Melina Schuh
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Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction
Muscle function depends on a highly organized array of actin and myosin filaments. Butkevichet al. identify the C. elegansdrebrin-like protein DBN-1 as an important regulator of actin filament stability in muscle cells, which relocalises from M-lines to I-bands on contraction.
- Eugenia Butkevich
- , Kai Bodensiek
- & Dieter R. Klopfenstein
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Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing
Adherent cells actively probe the rigidity of their substrates. Guptaet al. show that actin cytoskeleton rheology transitions from fluid to solid with increased substrate stiffness along with an isotropic to nematic ordering, implicating the remodelling of the whole actin network in rigidity sensing.
- Mukund Gupta
- , Bibhu Ranjan Sarangi
- & Benoît Ladoux
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Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization
As metastasis requires cellular machinery of migration and invasion, interfering with these functions is a promising anticancer strategy. Here the authors show that a structurally novel fascin inhibitor blocks filopodia formation, migration and invasion, and effectively inhibits metastasis in mice.
- Fang-Ke Huang
- , Shaoqin Han
- & Xin-Yun Huang
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Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome
Mutations in genes affecting intraflagellar transport account for some but not all cases of short rib polydactyly syndromes. Here Taylor et al. use whole exome sequencing and in vivo cell line assays to identify novel disease associated mutations in DYNC2LI1.
- S. Paige Taylor
- , Tiago J. Dantas
- & Deborah Krakow
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| Open AccessCdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation
Centrosome separation, promoted by the kinesin Eg5, is antagonized by the guanine nucleotide exchange factor Tiam1 through an unknown mechanism. Here Whalley et al. show that Tiam1 is phosphorylated by cyclin-dependent kinase 1 in prophase, leading to downstream activation of p21-activated kinases (PAKs).
- Helen J. Whalley
- , Andrew P. Porter
- & Angeliki Malliri
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| Open AccessMicrotubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth
Loss of the structural microtubule-associated protein 6 (MAP6) leads to neuronal differentiation defects that are independent of MAP6’s microtubule-binding properties. Here the authors establish a functional link between MAP6 and Semaphorin 3E signalling for proper formation of the fornix of the brain.
- Jean-Christophe Deloulme
- , Sylvie Gory-Fauré
- & Annie Andrieux
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| Open AccessVimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding
Vimentin is an intermediate filament protein that is targeted by oxidative modification at its single cysteine residue, C328. Here Pérez-Sala et al. reveal a role for this cysteine in vimentin organization and function, and uncover a protective role for zinc binding in filament stability.
- Dolores Pérez-Sala
- , Clara L. Oeste
- & F. Javier Cañada
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Loss of kinesin-14 results in aneuploidy via kinesin-5-dependent microtubule protrusions leading to chromosome cut
Loss of the motor protein kinesin-14 can lead to aneuploidy, but the mechanism is not known. Here the authors show that loss of kinesin-14 in fission yeast leads to long spindle microtubule protrusions that push properly segregated chromosomes into the division site, leading to chromosome cut during cytokinesis.
- Viktoriya Syrovatkina
- & Phong T. Tran
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Article
| Open AccessPlatelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
During early platelet spreading a novel F-actin structure forms, called the actin nodule. Here Poulter et al.demonstrate that actin nodule formation depends on WASp and the Arp2/3 complex, and using super-resolution microscopy they show that nodules bear a structural resemblance to podosomes.
- Natalie S. Poulter
- , Alice Y. Pollitt
- & Steven G. Thomas
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Article
| Open AccessCapping protein integrates multiple MAMP signalling pathways to modulate actin dynamics during plant innate immunity
Cytoskeletal remodelling is an important component of the innate immune response in plants. Here, Li et al. demonstrate that pathogen-triggered actin remodelling is due to the inhibition of capping protein (CP), and show that CP is required for resistance against plant pathogens.
- Jiejie Li
- , Jessica L. Henty-Ridilla
- & Christopher J. Staiger
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| Open AccessAMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation
Lipid droplets (LDs) supply fatty acids to cellular processes and move bidirectionally on microtubules. Here the authors show that nutrient starvation causes dispersal of mitochondria and LD to the periphery of the cell along detyrosinated microtubules and increases LD–mitochondria interactions in an AMPK-dependent manner.
- Albert Herms
- , Marta Bosch
- & Albert Pol
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| Open AccessSingle-molecule imaging of a three-component ordered actin disassembly mechanism
The roles of Coronin, Cofilin and AIP1 in promoting actin disassembly have not been well understood. Here using single-molecule fluorescence imaging, Jansen et al. show that the three proteins act together in a coordinated, temporal pathway to induce rapid severing and disassembly of actin filaments.
- Silvia Jansen
- , Agnieszka Collins
- & Bruce L. Goode
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The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+ stem cells
Colitis is a common human disorder but the clinical interventions are limited as the pathological mechanisms are not very clear. Here the authors find an elevated expression of non-muscle-myosin-II heavy chain Myh9 in a colitis mouse model, and show that Myh9 expression reduction or activity inhibition ameliorates epithelial injuries.
- Bing Zhao
- , Zhen Qi
- & Ye-Guang Chen
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Article
| Open AccessThe structure of FMNL2–Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation
FMNL formins polymerize actin filaments to generate cellular protrusions such as lamellipodia and filopodia at the leading edge of a cell. Here the authors provide detailed mechanistic insights into the formation of actin-based protrusions through GTPase dependent activation and membrane localization of FMNL1 and FMNL2.
- Sonja Kühn
- , Constanze Erdmann
- & Matthias Geyer
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Length regulation of mechanosensitive stereocilia depends on very slow actin dynamics and filament-severing proteins
Auditory sensory hair cells detect sounds by deflection of their actin-based stereocilia, which vary in length. By inducing expression of GFP-actin in mouse hair cells in vivo, Narayanan et al. demonstrate that stereocilia length is regulated by very slow actin turnover, which is restricted to the tips.
- Praveena Narayanan
- , Paul Chatterton
- & Benjamin J. Perrin
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| Open AccessLive-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear
Precise control of stereocilia length by auditory hair cells is vital for normal hearing. Drummond et al. follow in real-time the incorporation of actin into these structures and show that while the actin core is remarkably stable, and actin polymerization is limited to their distal tips.
- Meghan C. Drummond
- , Melanie Barzik
- & Thomas B. Friedman
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Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking
Destabilizing the actin cytoskeleton induces the formation of primary cilia, but the mechanism is unknown. Here, Kim et al.show that activity of the transcriptional coactivators YAP/TAZ is regulated by actin remodelling factors, and YAP/TAZ activity correlates with ciliogenesis.
- Jongshin Kim
- , Haiin Jo
- & Joon Kim
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ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled
The actin regulator CapZIP has been shown to regulate ciliogenesis in a phosphorylation-dependent manner. Miyatake et al.show that the atypical MAP kinase ERK7 promotes ciliogenesis by phophorylating CapZIP, and that interactions between both proteins and Dishevelled are required for CapZIP phosphorylation.
- Koichi Miyatake
- , Morioh Kusakabe
- & Eisuke Nishida
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HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus
Many viruses take advantage of microtubule-dependent motor proteins to move through the cell. Malikov et al. show that HIV-1 recruits the kinesin-1 adaptor FEZ1, and that the opposing activities of kinesin-1 and dynein motors are both required for the transport of HIV-1 capsids towards the nucleus.
- Viacheslav Malikov
- , Eveline Santos da Silva
- & Mojgan H. Naghavi
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Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing
Microtubule-destabilizing drugs and oncolytic viruses are two unrelated approaches to battle cancer. Here the authors show that microtubule-destabilizing drugs potentiate the efficiency of oncolytic rhabdoviruses by altering the cytokine production and response of the tumour cells.
- Rozanne Arulanandam
- , Cory Batenchuk
- & Jean-Simon Diallo
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Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules
Alignment of chromosomes at the spindle equator involves two kinesin family molecular motors, Kid and CENP-E. Here, Iemura and Tanaka show differential contributions of these motors, whereby Kid promotes partial alignment before end-on microtubule attachment to chromosomes, and CENP-E promotes alignment when microtubules are stabilized.
- Kenji Iemura
- & Kozo Tanaka
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Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking
Secretory vesicles must cross a dense cortical actin network to dock and fuse with the plasma membrane. Papadopulos et al. reveal that, in neurosecretory cells, relaxation of this network acts as a 'casting net', driving tethered vesicles towards the plasma membrane.
- Andreas Papadopulos
- , Guillermo A. Gomez
- & Frederic A. Meunier
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A mechanically sensitive cell layer regulates the physical properties of the Arabidopsis seed coat
Mechanical signalling is an important regulator of plant development. Here, Creff et al.propose that the perception of mechanical signals in growing seeds by a specific cell layer in the seed coat controls the accumulation of gibberellic acid and links mechanical signals to the regulation of seed size.
- Audrey Creff
- , Lysiane Brocard
- & Gwyneth Ingram
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Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue
The ciliary margin of the eye functions as a source of multipotent progenitor cells in certain organisms but whether it plays this role in humans has not been easy to study. Here the authors culture human embryonic stem cells that self-organize into retinal tissue, and show that ciliary margin-like growth zones emerge from the developing human retinal tissue and contain stem cell niches.
- Atsushi Kuwahara
- , Chikafumi Ozone
- & Yoshiki Sasai
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Article
| Open AccessControl of cytoplasmic dynein force production and processivity by its C-terminal domain
Cytoplasmic dynein from the yeast S. cerevisiae behaves distinctly from mammalian dyneins, despite structural conservation. Here, Nicholas et al. identify a C-terminal domain in mammalian dynein that restricts force generation and travel distance, which, when removed, allows mammalian dynein to behave like its yeast counterpart.
- Matthew P. Nicholas
- , Peter Höök
- & Arne Gennerich
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Article
| Open AccessToll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor
Microbial pathogens can activate both innate and adaptive receptors, and integration of these signals may enhance the sensitivity of the immune response. Freeman et al. show that innate microbial cues sensitize B cells to antigen by increasing actin dynamics and reducing the actin-dependent confinement of the B-cell receptor.
- Spencer A. Freeman
- , Valentin Jaumouillé
- & Michael R. Gold
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Article
| Open AccessA proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Integrins are activated by many extracellular cues and respond by assembling diverse signalling complexes. Byron et al.use activation state-specific antibodies to proteomically characterize these complexes, and provide insight into integrin-dependent microtubule stabilization.
- Adam Byron
- , Janet A. Askari
- & Martin J. Humphries
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ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning
Protein kinase NEK8 is important for cilliary function, but the mechanism by which it acts is unknown. Czarnecki et al. identify the cilliary protein ANKS6 as a target and crucial activator of NEK8 and describe the importance of this protein interaction in embryonic development and organogenesis.
- Peter G. Czarnecki
- , George C. Gabriel
- & Jagesh V. Shah
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Article
| Open AccessTropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling
Insulin-stimulated GLUT4-storage vesicle fusion with the plasma membrane depends on activity of Akt2 and its downstream effectors. Here Lim et al.identify the actin-capping protein tropomodulin 3 as a novel Akt2 effector that remodels cortical actin to help facilitate GLUT4 membrane insertion.
- Chun-Yan Lim
- , Xuezhi Bi
- & Weiping Han
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Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT2R and cytoskeletal dysregulation
Increased levels of haematopoietic stem and progenitor cells in the blood have been linked to some forms of organ failure. Here, the authors show that the hormone angiotensin II increases mobilization of haematopoietic stem and progenitor cells by inducing cytoskeletal changes in bone marrow cells.
- Kyung Hee Chang
- , Ramesh C Nayak
- & Jose A Cancelas
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| Open AccessDirect evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia
Loss of olfactory function is one of the many symptoms of the ciliopathy Bardet–Biedl syndrome. Williams et al. show that Bardet–Biedl proteins are components of intraflagellar transport particles within cilia, and directly visualize their trafficking in native mammalian olfactory neurons.
- Corey L. Williams
- , Jeremy C. McIntyre
- & Jeffrey R. Martens
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Architecture and dynamic remodelling of the septin cytoskeleton during the cell cycle
In budding yeast, septin filaments adopt an hourglass structure at the bud neck that is remodelled into a double ring. Ong et al.reveal in fine detail the dynamic reorganization of septin filaments within these structures through the cell cycle using platinum-replica electron microscopy.
- Katy Ong
- , Carsten Wloka
- & Erfei Bi
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Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia
Our current understanding of cilia biology and ciliary diseases is incomplete, in part because cilia are hard to visualize. Here, the authors use cryo-electron tomography to image the structure of human cilia with high resolution and uncover the elusive ciliary defects in Primary Ciliary Dyskinesia patients.
- Jianfeng Lin
- , Weining Yin
- & Daniela Nicastro
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Cytoplasmic dynein transports cargos via load-sharing between the heads
Dynein is a microtubule-based motor protein, but the mechanism of how it generates force is not clear. Here, Belyy et al. use an optical trapping approach to measure force and conclude that the two dynein heads function through a unique load sharing mechanism allowing them to work against forces greater than an individual head.
- Vladislav Belyy
- , Nathan L Hendel
- & Ahmet Yildiz