Featured
-
-
Article
| Open AccessTCR ITAM multiplicity is required for the generation of follicular helper T-cells
The strength of TCR activation shapes T cell selection and differentiation. Here the authors show by modulating the number of activatory motifs in TCR complex that the strength of TCR signal is critical for the development of some T cell subsets but not for T cell effector functions or repertoire.
- SuJin Hwang
- , Amy C. Palin
- & Paul E. Love
-
Article |
IM30 triggers membrane fusion in cyanobacteria and chloroplasts
Thylakoid membranes are critical components of chloroplasts and cyanobacteria. Here, Hennig et al. demonstrate that IM30, a conserved chloroplast and cyanobacterial protein, binds to thylakoid membranes and can trigger membrane destabilization and fusion in a Mg2+dependent manner.
- Raoul Hennig
- , Jennifer Heidrich
- & Dirk Schneider
-
Article
| Open AccessExpression of the vault RNA protects cells from undergoing apoptosis
Cellular functions of the vault complex, a large ribonucleoprotein assembly remain elusive. Here, the authors show that Epstein–Barr virus infection enhances the expression of the vault complex-associated RNAs, which leads to improved survival of infected cells due to the inhibition of cell apoptosis.
- Melanie Amort
- , Birgit Nachbauer
- & Norbert Polacek
-
Article
| Open AccessTopological control of the Caulobacter cell cycle circuitry by a polarized single-domain PAS protein
The bacterium Caulobacter crescentus is a model organism for research on the bacterial cell cycle and cell division processes. Here, Sanselicio et al. show that the MopJ protein contributes to the control of cell cycle and growth in C. crescentus.
- Stefano Sanselicio
- , Matthieu Bergé
- & Patrick H. Viollier
-
Article
| Open AccessType I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells
Eomesodermin is the key transcription factor for the development of ‘virtual memory’ T cells that develop in the absence of antigen-driven activation. Here the authors show that type I interferons directly activate eomesodermin and contribute to the homeostasis of virtual memory CD8+T cells.
- Valérie Martinet
- , Sandrine Tonon
- & Stanislas Goriely
-
Article |
Clk post-transcriptional control denoises circadian transcription both temporally and spatially
CLOCK (CLK) is essential for the development and maintenance of circadian rhythms in Drosophila. Here, the authors show that Clk mRNA is regulated by miRNA bantam, and deletion of bantambinding site leads to stochastic CLK-driven transcription and development of the circadian neurons.
- Immanuel Lerner
- , Osnat Bartok
- & Sebastian Kadener
-
Article |
IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer
The NFκB signalling pathway is regulated through the formation of transcription factor dimers but mechanisms controlling their formation are poorly understood. Here, Tsui et al. report that IκBb is a positive regulator of Rel-NFκB dimer formation, using in vitro and in vivoexperiments and mathematical modelling.
- Rachel Tsui
- , Jeffrey D. Kearns
- & Alexander Hoffmann
-
Article
| Open AccessPrdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2
Neuron differentiation is marked by changes in intracellular redox status. Here Yan et al. show that ER-resident peroxiredoxin 4 senses increased H2O2and prevents the surface expression of differentiation-promoting GDE2 by modifying cysteine residues within GDE2.
- Ye Yan
- , Cynthia Wladyka
- & Shanthini Sockanathan
-
Article |
Sequential growth of long DNA strands with user-defined patterns for nanostructures and scaffolds
Assembling defined sequences of DNA is important for many applications, but the synthesis becomes more difficult as the target size increases. Here, the authors report a method for assembling DNA by combining smaller strands, with the final structure determined by the order of addition of the fragments.
- Graham D. Hamblin
- , Janane F. Rahbani
- & Hanadi F. Sleiman
-
Article |
Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis
Metastatic cells are thought to influence vascular permeability through secreted factors but the mechanisms are unclear. Here, the authors identify melanoma-secreted SPARC as a major regulator of cancer cell extravasation that modulates endothelial intercellular junctions.
- Mélanie Tichet
- , Virginie Prod’Homme
- & Sophie Tartare-Deckert
-
Article
| Open AccessThe NOXA–MCL1–BIM axis defines lifespan on extended mitotic arrest
Cells experiencing extended mitotic arrest often undergo cell death as a result of steadily declining levels of the apoptotic inhibitor MCL1, but the mechanism controlling this process is poorly understood. Here, Haschka et al.show that the BH3-only protein NOXA promotes the degradation of MCL1, enabling BIM-dependent cell death.
- Manuel D. Haschka
- , Claudia Soratroi
- & Luca L. Fava
-
Article |
Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling
Cochlear sensory hair cells produced during development are not replaced after loss so converting the surrounding supporting cells into hair cells could be a potential regenerative strategy. Here the authors show that hair cells can be directly generated from adjacent supporting cells in developing mouse embryos by inhibition of ephrin-B2 signalling.
- Jean Defourny
- , Susana Mateo Sánchez
- & Brigitte Malgrange
-
Article
| Open AccessA REDD1/TXNIP pro-oxidant complex regulates ATG4B activity to control stress-induced autophagy and sustain exercise capacity
Stress-induced macroautophagy is initiated by the induction of reactive oxygen species (ROS). Here Qiao et al.show that the mTOR inhibitor REDD1 in a complex with pro-oxidant protein TXNIP induces ROS formation, leading to ATG4B suppression and autophagy activation in a largely mTOR-independent manner.
- Shuxi Qiao
- , Michael Dennis
- & Leif W. Ellisen
-
Article
| Open AccessFGF1 and FGF19 reverse diabetes by suppression of the hypothalamic–pituitary–adrenal axis
Fibroblast growth factor (FGF) family proteins have anti-diabetic effects, but how they work is currently unclear. Here the authors show that injections of FGF1 or FGF19 into the brain of diabetic rats alter glucose and lipid homeostasis by suppressing activity of the hypothalamic-pituitary-adrenal signalling axis.
- Rachel J. Perry
- , Sangwon Lee
- & Gerald I. Shulman
-
Article |
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes
dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here the authors report that dDsk2 regulates RNA polymerase II pausing by preventing H2Bub1 deubiquitylation, suggesting a nonproteolytic function of dDsk2.
- Roman Kessler
- , Johan Tisserand
- & Fernando Azorín
-
Article |
In vivo model with targeted cAMP biosensor reveals changes in receptor–microdomain communication in cardiac disease
cAMP is a second messenger that acts in distinct intracellular locations regulating diverse cellular functions. Here the authors design a FRET-based cAMP biosensor and use it to measure in vivodynamics of cAMP concentration changes in the sarcoplasmatic reticulum of mouse cardiomyocytes in health and disease.
- Julia U. Sprenger
- , Ruwan K. Perera
- & Viacheslav O. Nikolaev
-
Article |
Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells
Lineage establishment of theca cells is essential for follicle development and morphogenesis of the ovary. Here the authors provide genetic evidence for the origins of theca progenitor cells and study the mechanisms critical for their differentiation.
- Chang Liu
- , Jia Peng
- & Humphrey H.-C. Yao
-
Article |
Galanin modulates the neural niche to favour perineural invasion in head and neck cancer
Perineural invasion occurs in many head and neck cancers and is thought to be an active process where tumour cells degrade the neural sheath. Here the authors show that the neuropeptide galanin mediates the crosstalk between nerves and cancer cells to promote malignant progression.
- Christina Springstead Scanlon
- , Rajat Banerjee
- & Nisha J. D’Silva
-
Article |
Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling
The bimodal switch model posits that the unliganded thyroid hormone receptor (TR) binds chromatin stably. Here, the authors demonstrate ligand dependent recruitment of TR to chromatin, and further show that both unliganded and ligand-bound TR engages with chromatin in a highly dynamic manner.
- Lars Grøntved
- , Joshua J. Waterfall
- & Sheue-yann Cheng
-
Article |
Heparanase is a host enzyme required for herpes simplex virus-1 release from cells
Herpesviruses bind to heparan sulphate (HS) on the surface of cells before infecting them. Here, the authors show that heparanase, a host enzyme that degrades HS and is upregulated on viral infection, is required for the release of newly formed viruses from infected cells.
- Satvik R. Hadigal
- , Alex M. Agelidis
- & Deepak Shukla
-
Article |
The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence
Oncogene-induced senescence (OIS) is a barrier to tumour progression. Here the authors identify the long non-coding RNA MIR31HG as a regulator of cellular senescence using the oncogene-induced senescence triggered by B-RAF expression in immortalized fibroblasts.
- Marta Montes
- , Morten M. Nielsen
- & Anders H. Lund
-
Article
| Open AccessUbiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization
The relaying of Wnt signals to the cytoplasm requires the formation of signalosomes through the reversible polymerization of Dishevelled (Dvl). Here the authors establish the functional consequences of ubiquitination of the Dvl DIX domain and identify deubiquitinases predicted to promote Dvl polymerization.
- Julia Madrzak
- , Marc Fiedler
- & Jason W. Chin
-
Article |
REGγ is critical for skin carcinogenesis by modulating the Wnt/β-catenin pathway
REGγ, a proteasome activator, is associated with multiple oncogenic pathways in human cancers and can promote the degradation of multiple proteins including p53. Here the authors highlight a potential role for REGγ in skin cancer and propose a molecular mechanism linking p38 MAPK and Wnt signalling.
- Lei Li
- , Yongyan Dang
- & Xiaotao Li
-
Article
| Open AccessC-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle
SHGC syndrome affects cattle and has clinical features similar to human Seckel syndrome. Here Floriot et al. identify the causative mutation in the centrosomal protein C-Nap1 that affects centriole cohesion and cell migration, extending the range of loci involved in human Seckel-like syndromes.
- Sandrine Floriot
- , Christine Vesque
- & Laurent Schibler
-
Article |
Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
Differentiation of embryonic stem cells (ESCs) into neural lineages involves epigenetic changes. Here the authors show that transient histone deacetylation promotes the transition from epiblast stem cells to neural progenitors during mouse ESC differentiation and show that this effect is partly mediated by the restriction of Nodal signalling by histone deacetylase 1.
- Pingyu Liu
- , Xiaoyang Dou
- & Naihe Jing
-
Article |
Coupled local translation and degradation regulate growth cone collapse
Local protein translation regulates growth cone dynamics in response to guidance cues. Here the authors show that locally translated proteins are the main targets of the ubiquitin-proteasome system, and that local signalling promotes the ubiquitination and degradation of RhoA, leading to growth cone collapse.
- Alessia Deglincerti
- , Yaobin Liu
- & Samie R. Jaffrey
-
Article |
Regulation of endogenous transmembrane receptors through optogenetic Cry2 clustering
Signaling through transmembrane receptors regulates diverse biological processes including cell proliferation, motility and differentiation. Here, the authors demonstrate the optogenetic control of endogenous transmembrane receptor activity through clustering using a new modular strategy.
- L. J. Bugaj
- , D. P. Spelke
- & D. V. Schaffer
-
Article |
LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis
Wnt signalling can be transmitted both through a canonical pathway, via the co-receptors LRP5/6, and through Frz in a non-canonical pathway. Here, the authors demonstrate a direct interaction between Frz and LRP5/6, describing a new mechanism for how these receptors are primed to respond to Wnt ligands.
- Dan-ni Ren
- , Jinxiao Chen
- & Weidong Zhu
-
Article
| Open AccessASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
The human protein APOBEC3G (A3G) inhibits HIV-1 replication, but the viral protein Vif counteracts by inducing A3G degradation. Here Miyakawa et al. show that the antiretroviral drug AZT restores A3G function in vitroby stimulating expression of a host protein, ASK1, which interferes with the action of Vif.
- Kei Miyakawa
- , Satoko Matsunaga
- & Akihide Ryo
-
Article |
Regulated delivery of molecular cargo to invasive tumour-derived microvesicles
Cells shed various types of vesicles differing in size and content. Here the authors show that cancer cells utilize VAMP3-mediated traffic to deliver MT1-MMP to surface microvesicles and facilitate amoeboid-like cell invasion, with VAMP3-containing vesicles also found in body fluids of cancer patients.
- James W. Clancy
- , Alanna Sedgwick
- & Crislyn D’Souza-Schorey
-
Article
| Open AccessDynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids
Recent data question the long-assumed link between caveolae and endocytosis of membrane proteins. Shvets et al. use genome editing to tag and trace endogenous caveolar proteins, providing evidence that these structures exclude membrane proteins and are instead required for proper sorting of excess membrane lipids.
- Elena Shvets
- , Vassilis Bitsikas
- & Benjamin J. Nichols
-
Article
| 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
-
Article |
Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest
Mammalian female meiosis is error prone, with error rates increasing with age. Here Touati et al. show that the spindle assembly checkpoint (SAC) protein BubR1, which decreases with age, has multiple roles in meiosis I by controlling SAC, stabilizing the mitotic spindle and timing the onset of anaphase I.
- Sandra A. Touati
- , Eulalie Buffin
- & Katja Wassmann
-
Article |
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
-
Article
| Open AccessOsmosensing and scaffolding functions of the oligomeric four-transmembrane domain osmosensor Sho1
The yeast high osmolarity glycerol pathway activates the Hog1 MAP kinase via two branches, SLN1 and SHO, but the identity of the osmosensor has only been shown for the SLN1 branch. Here the authors demonstrate that the four-TM domain protein Sho1 functions as both an osmosensor and adaptor protein necessary for Hog1 activation.
- Kazuo Tatebayashi
- , Katsuyoshi Yamamoto
- & Haruo Saito
-
Article
| Open AccessA STIM2 splice variant negatively regulates store-operated calcium entry
STIM proteins sense calcium depletion in the endoplasmic reticulum and in response activate calcium influx through Orai1 channels located at the plasma membrane. Here, Miederer et al. identify a novel splice variant of STIM2 that fails to interact with and activate Orai1 and may act to fine-tune cellular calcium homeostasis by negatively regulating calcium influx.
- Anna-Maria Miederer
- , Dalia Alansary
- & Barbara A. Niemeyer
-
Article
| Open AccessTracing the evolutionary origins of insect renal function
The evolution of neuropeptide signalling in insects is poorly understood. Here the authors map renal tissue architecture in the major insect Orders, and show that while the ancient neuropeptide families are involved in signalling in nearly all species, there is functional variation in the cell types that mediate the signal.
- Kenneth A. Halberg
- , Selim Terhzaz
- & Julian A. T. Dow
-
Article |
Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal
Abstinent smokers experience affective withdrawal symptoms that contribute to relapse, yet the circuitry and mechanisms underlying these symptoms are unknown. Here the authors identify a critical role for a ventral tegmental area-habenula-interpeduncular circuit in nicotine withdrawal-induced anxiety.
- Rubing Zhao-Shea
- , Steven R. DeGroot
- & Andrew R. Tapper
-
Article
| Open AccessA single cyclin–CDK complex is sufficient for both mitotic and meiotic progression in fission yeast
It was recently shown that a single cyclin–CDK complex is sufficient to drive mitosis in fission yeast. Here, the authors show that this complex is also sufficient for meiotic progression, suggesting that specialized complexes are not required for the more intricate transitions of meiosis.
- Pilar Gutiérrez-Escribano
- & Paul Nurse
-
Article |
Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death
Cancer cells have elevated levels of reactive oxygen species. Here the authors show that cancer cells can be selectively killed in vitro and in vivoby an oxidative stress-activated drug, which amplifies the generation of reactive oxygen species while blocking the cells’ antioxidant defense.
- Joungyoun Noh
- , Byeongsu Kwon
- & Dongwon Lee
-
Article
| Open AccessTonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals
A simple model for receptor number–function relationships dictates a positive correlation between receptor content and ligand effect. Here, the authors demonstrate that the degree of type-1 cannabinoid receptor (CB1)-modulated GABA release cannot be predicted from CB1content of axon terminals.
- Nora Lenkey
- , Tekla Kirizs
- & Zoltan Nusser
-
Article
| Open AccessExtracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion
MRP8/14 are actively secreted by myeloid cells during inflammation. Here the authors show that MRP8/14 play an important role in leukocyte recruitment to the inflammatory site, triggering an autocrine cascade that promotes neutrophil adhesion to the endothelium.
- Monika Pruenster
- , Angela R. M. Kurz
- & Markus Sperandio
-
Article
| Open AccessRadixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory
Lateral diffusion of receptors between synaptic and extrasynaptic sites is known to mediate plasticity. Hausrat et al. show that diffusion of α5-containing GABAAreceptors is controlled by phosphorylation of the extrasynaptic anchoring protein Radixin, and reveal a role for Radixin in learning and memory.
- Torben J. Hausrat
- , Mary Muhia
- & Matthias Kneussel
-
Article
| Open AccessSingle-molecule chemo-mechanical unfolding reveals multiple transition state barriers in a small single-domain protein
Although most protein folding experiments can be explained by a single pathway, theoretical evidence suggests the presence of multiple pathways. Here, the authors resolve this using a combination of force, chemical denaturation and mutagenesis to modulate the flux between parallel pathways.
- Emily J. Guinn
- , Bharat Jagannathan
- & Susan Marqusee
-
Article |
Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3
Fruit flies have eight insulin-like peptides (Dilps), whose regulation and function is largely unexplored. Here the authors show that, whereas dietary amino acids promote secretion of Dilp2, sugar-dependent release of the glucagon-related hormone AKH drives Dilp3 secretion.
- Jung Kim
- & Thomas P. Neufeld
-
Article |
Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity
Phosphorylation of insulin receptor substrate (IRS)-1/2 by insulin-like growth factor (IGF)-I receptor tyrosine kinase is essential for IGF signalling. Here, the authors show that monoubiquitination of IRS-2 by the ubiquitin ligase Nedd4 recruits IRS-2 to the cell membrane and increases IRS-2 phosphorylation and IGF signalling.
- Toshiaki Fukushima
- , Hidehito Yoshihara
- & Shin-Ichiro Takahashi
-
Article |
Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage
Chaperone-mediated autophagy (CMA) helps maintain protein quality during cellular stress. Here the authors show that CMA is also activated in response to DNA damage and regulates degradation of the cell cycle regulator Chk1—the first nuclear protein shown to be a substrate of CMA.
- Caroline Park
- , Yousin Suh
- & Ana Maria Cuervo
-
Article |
Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways
Aging leads to impaired differentiation and increased pool size of hematopoietic stem cells (HSCs). Here, the authors show that wild-type p53-induced phosphatase 1 (Wip1), a negative regulator of DNA damage response pathways, regulates aging-associated HSC differentiation and expansion viap53 and mTORC1 pathways, respectively.
- Zhiyang Chen
- , Weiwei Yi
- & Zhenyu Ju
-
Article |
Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex
Tuberous sclerosis complex (TSC) arises from mutations in an activator of the small GTPase Rheb. Here the authors show that syntenin binds to GDP-bound Rheb, and loss of this interaction in TSC leads to increased syntenin expression and downstream signalling defects leading to aberrant spine synapse morphogenesis.
- Hiroko Sugiura
- , Shin Yasuda
- & Kanato Yamagata
Browse broader subjects
Browse narrower subjects
- Autophagy
- Cell adhesion
- Cell death
- Cell division
- Cell growth
- Cell migration
- Cell polarity
- Cell signalling
- Cellular imaging
- Chromosomes
- Circadian rhythms
- Cytoskeleton
- Glycobiology
- Mechanisms of disease
- Membrane trafficking
- Nuclear organization
- Nuclear transport
- Organelles
- Post-translational modifications
- Protein folding
- Protein transport
- Proteolysis
- Senescence