Featured
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Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks
Processes that regulate the mechanical and dynamic properties of actin cytoskeleton are important for multiple eukaryotic cell functions. In this study, using reconstituted crosslinked actin networks, organization is found to be determined by the competing kinetics of actin gelation and bundle formation.
- Tobias T. Falzone
- , Martin Lenz
- & Margaret L. Gardel
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Article
| Open AccessThe Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility
The non-canonical Wnt signalling pathway mediates cell migration via the GTPase Rac but the detailed mechanism is unclear. In this study, the Daple protein is shown to regulate Wnt5a mediated activation of Rac, resulting in the formation of lamellipodia and cell migration.
- Maki Ishida-Takagishi
- , Atsushi Enomoto
- & Masahide Takahashi
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Microtubule and cortical forces determine platelet size during vascular platelet production
Platelets are formed from megakaryocytes but the exact mechanisms are unknown. Thonet al.describe circular preplatelets and barbell shaped proplatelets in human blood and demonstrate, with the aid of a mathematical model, a role for microtubule-based forces in regulating final platelet size.
- Jonathan N Thon
- , Hannah Macleod
- & Joseph E. Italiano Jr
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Article
| Open AccessActivin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors
Signalling inputs to neural progenitors regulate the differentiation of the stem cell pool. By analysing the mechanisms occuring during neurogenesis, Cambrayet al. report that activin is the pivotal factor regulating the differentiation of telencephalic neural precursors towards a cortical interneuron fate.
- Serafí Cambray
- , Charles Arber
- & Tristan A. Rodríguez
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A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response
The bone morphogenetic protein (BMP) and Smad1 signalling pathway is required for embryogenesis. In this study, Smad1 is shown to be phosphorylated by Atm in response to DNA damage and this results in elevated Smad1 signalling, thus uncovering a new role for this pathway in the DNA damage response.
- Jenny Fung Ling Chau
- , Deyong Jia
- & Baojie Li
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Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression
Tumour cells are subject to replication stress but how cells overcome damage without inducing senescence and apoptotic pathways is unclear. Here, the authors study polyploidy in cancer cells and show that this blocks apoptotic and senescent pathways, resulting in the induction of proteins involved in DNA repair.
- Li Zheng
- , Huifang Dai
- & Binghui Shen
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Article
| Open AccessThe Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2
Mitochondrial dynamics and trafficking are important for providing energy for neuron function. In this study, the Armadillo repeat containing proteins clustered on the X chromosome are shown to be highly expressed in the nervous system and have a role in mitochondrial dynamics.
- Guillermo López-Doménech
- , Román Serrat
- & Eduardo Soriano
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Article
| Open AccessJAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency
Culture conditions are critical for the successful induction of pluripotent stem cells and define whether cells are primed or naïve. Here, activation of JAK/STAT3 signalling is shown to be sufficient and dominant over antagonistic cues to enable the induction of a naïve pluripotent state in stem cells.
- Anouk L. van Oosten
- , Yael Costa
- & José C.R. Silva
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Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm
Humans and rodents normally store more urine in the bladder when fast asleep than when awake. In this study, the production of the gap junction protein connexin43, a regulator of bladder capacity, is shown to oscillate in mouse urinary bladder muscle in synchrony with the circadian clock.
- Hiromitsu Negoro
- , Akihiro Kanematsu
- & Osamu Ogawa
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Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics
Studying the effects of extracellular matrix stiffening has been impeded because mostin vitromodels are static. Here, dynamic hydrogels are developed that stiffen in the presence of cells and are used to investigate the short-term (minutes-to-hours) and long-term (days-to-weeks) cellular responses to dynamic stiffening.
- Murat Guvendiren
- & Jason A. Burdick
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miR-484 regulates mitochondrial network through targeting Fis1
Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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Article
| Open AccessCYLD negatively regulates transforming growth factor-β-signalling via deubiquitinating Akt
Lung injury initiates a series of wound-healing responses, which if unregulated, can lead to fibrosis. Liet al. show that the deubquitinase CYLD has a key role in the prevention of fibrosis by inhibiting transforming growth factor β-signalling through the direct deubiquitination of the protein kinase Akt.
- Jae Hyang Lim
- , Hirofumi Jono
- & Jian-Dong Li
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Drosophila follicle stem cells are regulated by proliferation and niche adhesion as well as mitochondria and ROS
Stem cells are thought to be tethered in their niche via adhesion molecules and the inhibition of cell differentiation. Here, the authors screened for genes required for maintainingDrosophilaovarian follicle stem cells and found their function to depend on cell proliferation, mitochondrial function and niche adhesion.
- Zhu A. Wang
- , Jianhua Huang
- & Daniel Kalderon
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Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris
Endosomes contain hydrolytic enzymes, and recent reports have suggested that the endosomal membrane can be damaged by wear particles, resulting in the release of their contents and an inflammatory response. In this study, a role for annexin II in the repair of the damaged endosome membrane is reported.
- Brian Scharf
- , Cristina C. Clement
- & Laura Santambrogio
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Poly(ADP-ribose) controls DE-cadherin-dependent stem cell maintenance and oocyte localization
Drosophilagermline stem cells are anchored to their niche via DE-cadherin. In this study, poly(ADP-ribose) is shown to regulate the expression of DE-cadherin via the heterogeneous nuclear ribonucleoprotein, hnRNPA1, and defects in poly(ADP-ribose) catabolism or hnRNPA1 deficiency lead to the loss of germline stem cells.
- Yingbiao Ji
- & Alexei V. Tulin
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Casein kinase 2 reverses tail-independent inactivation of kinesin-1
Kinesin-1 is a motor protein that transports cargo along microtubules and defects in this process can result in neurodegeneration. In this study, a role for casein kinase 2 in regulating the activity of Kinesin-1 is reported, suggesting that signalling molecules can modulate this transport process.
- Jing Xu
- , Babu J. N. Reddy
- & Steven P. Gross
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Article
| Open AccessFAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure
Lysine-specific demethylase 1 (LSD1) removes methyl groups from mono-methylated and dimethylated lysine 4 of histone H3 and represses transcription. In this study, a role for LSD1 in the regulation of genes involved in energy expenditure in adipocytes is reportedin vitroand in mice fed on a high-fat diet.
- Shinjiro Hino
- , Akihisa Sakamoto
- & Mitsuyoshi Nakao
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FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis
FAT-10 targets proteins for degradation in a ubiquitin-independent manner and NUB1L accelerates this process. In this study, both FAT-10 and NUB1L are shown to interact with the VWA domain of the Rpn10 subunit of the 26S proteasome, suggesting that this is a receptor site for ubiquitin-like modifiers.
- Neha Rani
- , Annette Aichem
- & Marcus Groettrup
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| Open AccessActivation of canonical Wnt signalling is required for TGF-β-mediated fibrosis
Aberrant activation of the TGF-β pathway leads to fibrotic disease. Distler and colleagues show that TGF-β-mediated fibrosis requires the decrease of Dickkopf-1, an antagonist of canonical Wnt signalling, suggesting that the two pathways interact for the manifestation of this disease.
- Alfiya Akhmetshina
- , Katrin Palumbo
- & Jörg H.W. Distler
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Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release
Accumulation of lysosomal lipids is a feature of Niemann'-Picks (NP) disease, but how these lipids contribute to the disease is unclear. In this study, calcium released via the lysosomal TRPML1 channel is shown to be reduced in NP-type C cells, and sphingomyelins are found to inhibit the channel's activity.
- Dongbiao Shen
- , Xiang Wang
- & Haoxing Xu
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Sensitivity control through attenuation of signal transfer efficiency by negative regulation of cellular signalling
How the sensitivity of biological and pharmacological signalling responses is controlled is poorly understood. Here, computational analyses and cellular experiments show that the sensitivity of a simple biochemical reaction to activators and inhibitors is controlled by negative regulation of cellular signalling.
- Yu Toyoshima
- , Hiroaki Kakuda
- & Shinya Kuroda
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| Open Accessγ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor
Glutathione's key role as a modulator of reactive oxygen species levels has recently been challenged. Quintana-Cabreraet al. now provide in vivoevidence supporting an antioxidant and neuroprotective function for γ-glutamylcysteine, which replaces glutathione by acting as glutathione peroxidase-1 cofactor.
- Ruben Quintana-Cabrera
- , Seila Fernandez-Fernandez
- & Juan P. Bolaños
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Three-dimensional imaging of single nanotube molecule endocytosis on plasmonic substrates
Imaging and tracking the motion of single molecules on cell plasma membranes requires high spatial resolution in three dimensions. Honget al. develop a plasmonic ruler based on the fluorescence enhancement of carbon nanotubes on a gold plasmonic substrate, allowing the observation of nanotube endocytosis in three dimensions.
- Guosong Hong
- , Justin Z. Wu
- & Hongjie Dai
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Interpolar microtubules are dispensable in fission yeast meiosis II
Interpolar microtubules were thought to be indispensable for eukaryotic cell division. Here, Akera and colleagues demonstrate that the second division of meiosis in yeast can occur in the absence of interpolar microtubules, and identify the forespore membrane as a force producing structure in cell division.
- Takashi Akera
- , Masamitsu Sato
- & Masayuki Yamamoto
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The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation
TLRs have a role in innate immunity and TLR4 recognizes lipopolysaccharide on the cell wall of Gram-negative bacteria. Now, Doyle and colleagues show that a transmembrane protein TMED7, similar to aDrosophilahomologue, can negatively control TLR4 signalling, suggesting a conserved role in innate immunity.
- Sarah L. Doyle
- , Harald Husebye
- & Anne F. McGettrick
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Article
| Open AccessTelomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
Irreparable DNA damage leads to apoptosis or senescence. Hewittet al. show that, in response to genotoxic or oxidative stress, DNA damage occurs predominantly at telomere associated foci, which accumulate with age in vivo, irrespective of telomerase activity.
- Graeme Hewitt
- , Diana Jurk
- & João F. Passos
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CPEB-mediated ZO-1 mRNA localization is required for epithelial tight-junction assembly and cell polarity
Zonal occludens and claudin form tight junctions near the apical surface of cells and are important in polarized epithelia. In this study, the translational regulatory sequence-specific RNA binding protein CPEB is shown to be required for the correct localization of zona occluden 1 mRNA in mammary epithelial cells.
- Kentaro Nagaoka
- , Tsuyoshi Udagawa
- & Joel D. Richter
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| Open AccessDynamics of anterior–posterior axis formation in the developing mouse embryo
Detailed analysis of axis development in mouse embryo has been limited. Morriset al. developed an in vitroculture technique that enables the real-time observation of an anterior visceral endoderm formation and show that cell marker asymmetry within the AVE subdomain dictates the direction of the AVE migration.
- Samantha A. Morris
- , Seema Grewal
- & Magdalena Zernicka-Goetz
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Spatial coordination between cell and nuclear shape within micropatterned endothelial cells
Actin filaments are involved in the modulation of nuclear shape and function, but mechanistic understanding of these processes is lacking. Versaevelet al. show that orientation and deformation of the nucleus are regulated by lateral compressive forces driven by tension in central actomyosin fibres.
- Marie Versaevel
- , Thomas Grevesse
- & Sylvain Gabriele
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Regulation of histone modification and chromatin structure by the p53–PADI4 pathway
PADI4 is an enzyme that converts arginine residues to citrulline. Here, Tanikawa and colleagues show that, in response to DNA damage, histone H4 and Lamin C are citrullinated in a p53 and PADI4-dependent manner andPadi4-dependent manner and Padi4 null mice are resistant to radiation-induced apoptosis in the thymus.
- Chizu Tanikawa
- , Martha Espinosa
- & Koichi Matsuda
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Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells
Mutations in parkin, an ubiquitin ligase, cause an inherited form of Parkinson's disease. Here, Jianget al. generate induced pluripotent stem cells from two patients with parkin mutations and find that neurons derived from the stem cells have defects in dopamine release, dopamine uptake and oxidative metabolism.
- Houbo Jiang
- , Yong Ren
- & Jian Feng
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EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex
The role of ephrin receptors in tumour development and progression has remained controversial. Liet al. show that kinase activation of ephrin-B3 inhibits non-small-cell lung cancer migration both in vitro and in vivo, which depends on a novel interacting partner, RACK 1, in a ternary complex with PP2A and Akt.
- Guo Li
- , Xiao-Dan Ji
- & Dong Xie
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| Open AccessImperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG
Beclin1 is a key regulator of VPS34-related processes, including autophagy. Liet al. solve the crystal structure of Beclin 1 CC domain, an antiparallel dimer that is rendered metastable by a series of a-d' pairings, which determines its ability to form distinct heterodimers either with Atg14L or UVRAG.
- Xiaohua Li
- , Liqiang He
- & Yanxiang Zhao
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Article
| Open AccessABL1 regulates spindle orientation in adherent cells and mammalian skin
A systematic approach for identifying the genes responsible for the regulation of spindle orientation in mammals has been lacking. Now, Matsumuraet al. perform a kinase-targeting RNAi screen and identify ABL1, which through the direct phosphorylation of NuMa, is a novel regulator of spindle orientation.
- Shigeru Matsumura
- , Mayumi Hamasaki
- & Fumiko Toyoshima
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c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
Osteoblast maturation is regulated by c-Src and IL-6, but how these signalling pathways are integrated is not known. Here c-Src is shown to induce 1GFBP5 in immature osteoblasts in a STAT3 and IL-6-dependent manner, in mature osteoblasts, which express lower levels of c-Src, this signalling is lost.
- Barbara Peruzzi
- , Alfredo Cappariello
- & Anna Teti
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Two rotating cilia in the node cavity are sufficient to break left–right symmetry in the mouse embryo
The left–right asymmetry of an organism is patterned during development and is determined by fluid flow created by the movement of cilia. In this study, the asymmetry is shown to be determined early after the movement of cilia is established and that only two rotating cilia are required for breaking symmetry.
- Kyosuke Shinohara
- , Aiko Kawasumi
- & Hiroshi Hamada
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Article
| Open AccessExistence of long-lasting experience-dependent plasticity in endocrine cell networks
Experience-dependent plasticity and functional adaptation are thought to be restricted to the central nervous and immune systems. This study shows that long-lasting experience-dependent plasticity is a key feature of endocrine cell networks, allowing improved tissue function and hormone output following repeat demand.
- David J. Hodson
- , Marie Schaeffer
- & Patrice Mollard
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Article
| Open AccessPKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.
- Eduard Stefan
- , Mohan K. Malleshaiah
- & Stephen W. Michnick
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Article
| Open AccessCompetition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
- Nigel M. Stapleton
- , Jan Terje Andersen
- & Gestur Vidarsson
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O-Linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell–matrix interactions
The modification of proteins with O-linked-N-acetylglucosamine causes regulation of multiple cellular processes. In this study, Sakaidani and colleagues identify an endoplasmic reticulum O-linked-N-acetylglucosamine transferase in Drosophilathat regulates the adhesion of epithelial cells to the extracellular matrix.
- Yuta Sakaidani
- , Tomoko Nomura
- & Tetsuya Okajima
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Article |
Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion
Herpesvirus glycoprotein D binds to nectin 1 and the herpes virus entry mediator protein on the surface of host cells. In this study, Zhanget al. report the crystal structure of glycoprotein D in complex with the immunoglobulin-like domains of nectin 1, which suggests that binding of glycoprotein D to nectin 1 prevents nectin 1 dimerization.
- Na Zhang
- , Jinghua Yan
- & George F Gao
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Article
| Open AccessGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.
- Hanshuo Zhang
- , Yang Hao
- & Jianzhong Jeff Xi
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Article
| Open AccessDendritic spine formation and synaptic function require neurobeachin
Most excitatory synapses in the brain are found on dendritic spines, but the mechanisms underlying synapse formation are poorly understood. Niesmannet al. investigate the role of neurobeachin in synaptogenesis, and find that its deletion leads to fewer spinous synapses and altered postsynaptic currents.
- Katharina Niesmann
- , Dorothee Breuer
- & Markus Missler
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Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway
Cell fusion is involved in many different cellular processes including the fusion of trophoblast cells in the placenta. Matsuuraet al. identify a role for the β-catenin signalling pathway in the regulation of the transcription factor GCM1 and therefore the fusion of syncytiotrophoblast cells.
- Ken Matsuura
- , Takafumi Jigami
- & Tetsu Akiyama
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Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses
Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.
- Tarun Kumar Bhatt
- , Sameena Khan
- & Amit Sharma
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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Article
| Open AccessExtrasynaptic vesicle recycling in mature hippocampal neurons
In the classical model, fast neuronal signalling occurs at specialized presynaptic terminals. Now, Ratnayakaet al. show that stimulus-driven fusion and recycling of synaptic vesicles can occur at axonal sites remote from conventional synapses. These findings have implications for dynamic forms of neuron–neuron communication.
- Arjuna Ratnayaka
- , Vincenzo Marra
- & Kevin Staras
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Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision
At light levels where both rods and cones are active, their signals converge into shared downstream retinal circuitry. Using HCN1 deficient mice, this study shows that the signals from cone photoreceptors are overwhelmed when rod output is not regulated, suggesting a mechanism for how these systems interact.
- Mathias W. Seeliger
- , Arne Brombas
- & Frank Müller
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Review Article |
Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction
Hair cells of the inner ear transduce vibrations of the basilar membrane into electrical signals by a process known as mechanotransduction. Recent advances in genetic and molecular tools have led to an improved understanding of mechanotransduction as Peng and colleagues summarize in this Review.
- Anthony W. Peng
- , Felipe T. Salles
- & Anthony J. Ricci
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