Featured
-
-
Article
| Open AccessCalcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain
While transcranical direct current stimulation (tDCS) is used in clinical setting, its cellular mechanism of action is unclear. Here, Hajime Hirase and colleagues visualize cellular response in mouse brain to tDCS and show robust astrocyte activation that coincide with plasticity changes.
- Hiromu Monai
- , Masamichi Ohkura
- & Hajime Hirase
-
Article
| Open AccessZbtb20 promotes astrocytogenesis during neocortical development
Astrocytes in the brain are derived from neural precursor cells (NPCs). Here, Motoshi Nagao and colleagues show that the transcription repressor Zbtb20 regulates astrocyte specification in the mouse neocortex.
- Motoshi Nagao
- , Toru Ogata
- & Yukiko Gotoh
-
Article
| Open AccessCiliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation
Primary cilia are highly conserved microtubule-based organelles that play essential roles in several cellular processes including osteogenesis. Here the authors show that intraflagellar protein IFT80 regulates osteoblast differentiation by balancing signalling though the canonical and non-canonical Hedgehog pathways.
- Xue Yuan
- , Jay Cao
- & Shuying Yang
-
Article
| Open AccessCajal bodies are linked to genome conformation
Nuclear bodies can nucleate at sites of active transcription and are beneficial for efficient gene expression. Here, the authors show that Cajal bodies, a prominent type of nuclear body, contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
- Qiuyan Wang
- , Iain A. Sawyer
- & Miroslav Dundr
-
Article
| Open AccessActin nucleation at the centrosome controls lymphocyte polarity
Cell polarity is marked by re-orientation of the centrosome, but the mechanisms governing centrosome polarization are poorly understood. Here Obino et al. show that in lymphocytes centrosome-associated Arp2/3 nucleates actin that tethers the centrosome to the nucleus; activation depletes Arp2/3 from the centrosome and frees it from the nucleus.
- Dorian Obino
- , Francesca Farina
- & Ana-Maria Lennon-Duménil
-
Article
| Open AccessA CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
Centrosome clustering allows survival of cells with amplified centrosomes at the cost of chromosome instability. Here, Chavali et al. show that the centrosome component CEP215 collaborates with the kinesin motor HSET both to maintain spindle poles connections and to cluster centrosomes.
- Pavithra L. Chavali
- , Gayathri Chandrasekaran
- & Fanni Gergely
-
Article
| Open AccessHaem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance
PGRMC1 binds to EGFR and cytochromes P450, and is known to be involved in cancer proliferation and in drug resistance. Here, the authors determine the structure of the cytosolic domain of PGRMC1, which forms a dimer via haem–haem stacking, and propose how this interaction could be involved in its function.
- Yasuaki Kabe
- , Takanori Nakane
- & Makoto Suematsu
-
Article
| Open AccessA conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation
The important MAPK family of signalling proteins is controlled by MAPK phosphatases (MKPs). Here, the authors report the structure of MKP7 bound to JNK1 and characterise the conserved MKP-MAPK interaction.
- Xin Liu
- , Chen-Song Zhang
- & Zhi-Xin Wang
-
Article
| Open AccessVersatile protein tagging in cells with split fluorescent protein
Tagging proteins with fluorescent proteins is a powerful method for both imaging and non-imaging applications. Here the authors use the eleventh β-strand of sfGFP and sfCherry as epitope tags for multicolour imaging and amplified signals by tandem arrangement; shortness of the tag enabled introduction into genomic loci using CRISPR/Cas9.
- Daichi Kamiyama
- , Sayaka Sekine
- & Bo Huang
-
Article
| Open AccessVCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation
Protein homeostasis is crucial for maintaining a variety of cellular functions. Here the authors show that valosin-containing protein and its cofactors regulate tubular ER formation and protein synthesis efficiency, thereby control dendritic spine formation in neurons.
- Yu-Tzu Shih
- & Yi-Ping Hsueh
-
Article
| Open AccessCellular forces and matrix assembly coordinate fibrous tissue repair
Planar in vitromodels for wound closure stress the role of lamellipodial protrusions and purse-string contraction. Here the authors develop a 3D biomimetic model for tissue repair and show a mode of stromal closure that relies on whole tissue deformations, cell migration and matrix deposition.
- Mahmut Selman Sakar
- , Jeroen Eyckmans
- & Christopher S. Chen
-
Article
| Open AccessPX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking
The molecular underpinning of autism is unclear. Here the authors show PX-RICS deficient mice exhibit autism-like social behavioural abnormalities and impaired GABAA receptor trafficking, and enhancing inhibitory synaptic transmission with a GABAAreceptor agonist ameliorate the behavioural deficits.
- Tsutomu Nakamura
- , Fumiko Arima-Yoshida
- & Tetsu Akiyama
-
Article
| Open AccessMapping the dynamics and nanoscale organization of synaptic adhesion proteins using monomeric streptavidin
The advent of fluorescence-based super-resolution microscopy has created a need for labeling strategies relying on small probes that minimally perturb protein function. Here the authors describe a labeling method that reduces protein tag and label sizes, allowing for accurate protein targeting and measurements of protein dynamics in tight cellular spaces.
- Ingrid Chamma
- , Mathieu Letellier
- & Olivier Thoumine
-
Article
| Open AccessPerinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments
Cell migration through micrometric constraints is limited by low deformability of the nucleus. Here the authors show that in dendritic cells a perinuclear actin network nucleated by Arp2/3 increases nuclear deformation and allows the cells to pass through narrow constrictions, likely by rupturing the nuclear lamina.
- Hawa-Racine Thiam
- , Pablo Vargas
- & Matthieu Piel
-
Article
| Open AccessStabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration
Phosphatidylserine and its receptors are associated with cell-cell fusion. Here, the authors show the phosphatidylserine receptor stabilin-2 is expressed by muscle cells and plays a vital role in myoblast fusion and post-injury muscle regeneration in mice.
- Seung-Yoon Park
- , Youngeun Yun
- & In-San Kim
-
Article
| Open AccessStability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium
The Akt pathway integrates multiple signals, but whether it affects vasculature function is debatable. Here the authors show that Akt pathway shutdown in adult mouse endothelium causes destabilization of vasculature leading to cardiac and retinal dysfunction, due to decreased levels of Jagged1 and impaired Notch signaling.
- Bethany A. Kerr
- , Xiaoxia Z. West
- & Tatiana V. Byzova
-
Article
| Open AccessPromotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults
Mitochondrial dysfunction occurs in Parkinson's disease, although the underlying mechanisms are unclear. Here, the authors find necdin works to stabilise the mitochondrial regulator PGC-1α, and that overexpression of necdin protects against MPTP-mediated neurodegeneration both in vitro and in vivo.
- Koichi Hasegawa
- , Toru Yasuda
- & Kazuaki Yoshikawa
-
Article
| Open AccessCCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
Low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis. Here, the authors show that components of the CCC-protein complex, CCDC22 and COMMD1, facilitate the endosomal sorting of LDLR and that mutations in these genes cause hypercholesterolemia in dogs and mice, providing new insights into regulation of cholesterol homeostasis.
- Paulina Bartuzi
- , Daniel D. Billadeau
- & Bart van de Sluis
-
Article
| Open AccessIL-15-dependent balance between Foxp3 and RORγt expression impacts inflammatory bowel disease
Transcription factors directing T cell fate are induced by instructive signals such as cytokines. Here the authors show that IL-15 promotes Foxp3 and inhibits RORγt expression in CD4 T cells, and that IL-15 is critical to suppress colitis by maintaining the Treg to Th1/Th17 ratio in a mouse model.
- Milena J. Tosiek
- , Laurence Fiette
- & Antonio A. Freitas
-
Article
| Open AccessThe TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model
Dysregulation of microRNAs has been implicated in neurodevelopmental disorders, including schizophrenia. Here the authors show that the TLX-miR-219 cascade regulates the proliferation of neural stem cells during normal development, and this pathway is dysregulated in a schizophrenia iPSC model.
- Kiyohito Murai
- , Guoqiang Sun
- & Yanhong Shi
-
Article
| Open Accessαv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells
Integrins can regulate antigen-specific and innate immune receptor signalling, thereby affecting immune cell function. Here the authors show that avß3 integrin controls Toll-like receptor (TLR) signalling by regulating its trafficking to limit TLR-mediated B-cell proliferation and antibody production.
- Mridu Acharya
- , Anna Sokolovska
- & Adam Lacy-Hulbert
-
Article
| Open AccessInterphase APC/C–Cdc20 inhibition by cyclin A2–Cdk2 ensures efficient mitotic entry
The Anaphase Promoting Complex/Cyclosome (APC/C) and its co-activator Cdc20 regulate mitotic progression, but both are also present in interphase. Here Hein and Nilsson show that Cyclin A2–CDK2 phosphorylates Cdc20 to inhibit APC/C–Cdc20 activity during this cell cycle phase to promote mitotic entry.
- Jamin B. Hein
- & Jakob Nilsson
-
Article
| Open AccessThree mechanisms control E-cadherin localization to the zonula adherens
E-cadherin is an adhesion molecule mediating cell-cell adhesion; correct localization is important but how localization is controlled is not clear. Here the authors use Drosophilaas a model system to distinguish three distinct trafficking pathways that direct E-cadherin to the zonula adherens.
- Innokenty Woichansky
- , Carlo Antonio Beretta
- & Veit Riechmann
-
Article
| Open AccessThe unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles
In addition to their role in apoptosis, caspases are also involved in mediating non-apoptotic events. Here the authors show that the Drosophilamyosin family member CRINKLED and its mammalian counterpart act as substrate adaptor that facilitate caspase-mediated cleavage and localised kinase activity.
- Mariam H. Orme
- , Gianmaria Liccardi
- & Pascal Meier
-
Article
| Open AccessG9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression
The histone methyltransferase G9a methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors. Here, Zhang et al. show that methylation of ERα by G9a recruits the PHF20/MOF complex that deposits histone H4K16 acetylation promoting active transcription.
- Xi Zhang
- , Danni Peng
- & Xiaobing Shi
-
Article
| Open AccessG protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination
The molecular mechanism controlling oligodendrocyte differentiation is not fully understood. Here the authors show that G protein coupled receptor 37 acts as a negative regulator of CNS myelination, and this effect is mediated by suppression of ERK signalling.
- Hyun-Jeong Yang
- , Anna Vainshtein
- & Elior Peles
-
Article
| Open AccessMICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration
Mitochondrial calcium uptake is a highly regulated process, and calcium overload can lead to cell death. Here, using knockout mouse model, the authors show that the mitochondrial calcium uniporter (MCU) regulator MICU1 is needed to prevent calcium overload and promotes survival under liver regeneration and postnatal adaptation-associated stress.
- Anil Noronha Antony
- , Melanie Paillard
- & György Hajnóczky
-
Article
| Open AccessFAM21 directs SNX27–retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus
Endosomes maintain cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Here the authors show that the SNX27-retromer-WASH complex acts as a hub to direct cargoes to the plasma membrane by blocking their transport to lysosomes and Golgi apparatus.
- Seongju Lee
- , Jaerak Chang
- & Craig Blackstone
-
Article
| Open AccessBcl-2 is a critical mediator of intestinal transformation
The anti-apoptotic protein Bcl-2 is selectively expressed in intestinal stem cells (ISCs). Here, the authors show that, in intestinal stem cells, Bcl-2 alleviates apoptotic priming induced by the loss of the tumour suppressor Apc in ISCs and that the absence of Bcl-2 or pharmacological blockade of Bcl-2 can inhibit the intestinal tumorigenesis driven by the Apc-loss.
- Maartje van der Heijden
- , Cheryl D. Zimberlin
- & Louis Vermeulen
-
Article
| Open AccessOpen-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation
The proteasome plays a key role in proteostasis by mediating the degradation of ubiquitinated substrates. Here the authors show that an open-gate mutant of the proteasome is hyperactive towards a subset of substrates and can effectively delay the accumulation of toxic protein aggregates.
- Won Hoon Choi
- , Stefanie A. H. de Poot
- & Min Jae Lee
-
Article
| Open AccessDual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation
Wnt/β-catenin signaling regulates oligodendrocyte (OL) development. Here the authors show that Tcf7l2, a β-catenin transcriptional partner,sequentially interacts with stage-specific partners to coordinate the transitions of differentiation initiation and maturation during OL development.
- Chuntao Zhao
- , Yaqi Deng
- & Q. Richard Lu
-
Article
| Open AccessThe Gq signalling pathway inhibits brown and beige adipose tissue
Brown and beige adipose tissues contribute to organismal energy expenditure by generating heat. Here, Klepac et al. survey G protein-coupled receptors in brown fat and show that Gq-coupled receptors inhibit expression of thermogenic proteins in mice and in human adipocytes.
- Katarina Klepac
- , Ana Kilić
- & Alexander Pfeifer
-
Article
| Open AccessMeta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.
- Sonja I. Berndt
- , Nicola J. Camp
- & Susan L. Slager
-
Article
| Open AccessCadherin-11 localizes to focal adhesions and promotes cell–substrate adhesion
Cadherins are typically involved in cell-cell adhesion, however cadherin-11 promotes cell migration through an undefined mechanism. Langhe et al.show that cadherin-11 mediates adhesion to the cell matrix at focal adhesions through interaction with syndecan-4.
- Rahul P. Langhe
- , Tetyana Gudzenko
- & Jubin Kashef
-
Article
| Open AccessA ligand-independent integrin β1 mechanosensory complex guides spindle orientation
During cell division, the orientation of the mitotic spindle is sensitive to forces exerted on the cell cortex. Here Petridou and Skourides show that such cues are sensed by a mechanosensory complex established on force activated integrin β1 independent of ligand binding.
- Nicoletta I. Petridou
- & Paris A. Skourides
-
Article
| Open AccessInductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells
It is unclear how the microenvironment of the aorta-gonad-mesonephros influences haematopoietic stem cell (HSC) production early in mouse development. Here, Souilhol et al. use an in vitroaggregate system as a tool to understand how several pathways, BMP, SCF and Shh, may regulate HSC production.
- Céline Souilhol
- , Christèle Gonneau
- & Alexander Medvinsky
-
Article
| Open AccessAMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B
The diabetes drug Metformin decreases hepatic glucose production and activates AMP-activated protein kinase (AMPK). Here the authors provide evidence that AMPK activation antagonizes glucagon signalling by activating PDE4B, lowering cAMP levels and decreasing PKA activation.
- M. Johanns
- , Y.-C. Lai
- & M H Rider
-
Article
| Open AccessA general approach to visualize protein binding and DNA conformation without protein labelling
Single-molecule imaging of protein-DNA association requires fluorescently labelled protein, which limits the protein concentration that can be used. Here the authors exploit protein induced fluorescent enhancement of DNA sparsely labelled with Cy3 to visualize protein binding and correlate it with changes in DNA conformation.
- Dan Song
- , Thomas G. W. Graham
- & Joseph J. Loparo
-
Article
| Open AccessThe acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis
The reprogramming of fibroblasts to pluripotent stem cells has been well documented but there is interest in identifying additional factors involved. Here, the authors perform a screen of human kinases and show that the bromodomain protein, BRD3R, can promote reprogramming and suggest a role for this factor in regulating mitosis.
- Zhicheng Shao
- , Ruowen Zhang
- & Kejin Hu
-
Article
| Open AccessCSF-contacting neurons regulate locomotion by relaying mechanical stimuli to spinal circuits
CSF-contacting neurons are known to project to locomotor CPGs although their relevance to active locomotion is unclear. Here, the authors show that these cells constitute a mechanosensory organ relying on PKD2L1 channels to detect spinal cord curvature and modulate locomotor frequency in freely moving animals.
- Urs Lucas Böhm
- , Andrew Prendergast
- & Claire Wyart
-
Article
| Open AccessThe HMGB1 protein induces a metabolic type of tumour cell death by blocking aerobic respiration
HMBG1 is a protein expressed in natural killer cells and is important in immunosurveillance. In this study, the authors show that HMGB1 binds to and inhibits PKM2, resulting in a block in aerobic glycolysis and ultimately cell death.
- Georg Gdynia
- , Sven W. Sauer
- & Wilfried Roth
-
Article
| Open AccessTwo-colour live-cell nanoscale imaging of intracellular targets
The intracellular applications of STED microscopy are limited by the availability of dyes. Here the authors develop a two-colour labelling strategy based on SiR and ATTO590 dyes, and apply their strategy to image various subcellular membrane compartments.
- Francesca Bottanelli
- , Emil B. Kromann
- & Joerg Bewersdorf
-
Article
| Open AccessNuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation
The transcription factor, serum response factor, SRF regulates critical smooth muscle (SM) contractile gene expression but what else controls SM differentiation is unclear. Here, Horita et al. demonstrate that nuclear PTEN acts with SRF at the transcriptional level to maintain the differentiated SM phenotype.
- Henrick Horita
- , Christina L. Wysoczynski
- & Mary C. M. Weiser-Evans
-
Article
| Open AccessFeedback regulation of apical progenitor fate by immature neurons through Wnt7–Celsr3–Fzd3 signalling
The switch from neurogenesis to gliogenesis in cortical development is only partially understood. Here the authors show that Wnt-Planar cell polarity signaling in immature cortical neurons activates Notch in neural progenitor cells, thereby tuning the timing of their fate decisions.
- Wei Wang
- , Yves Jossin
- & Andre M. Goffinet
-
Article
| Open AccessGenetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development
COBRA1 is a BRCA1-binding protein and, as part of the negative elongation factor, regulates RNA polymerase II pausing and transcription elongation. Here, the authors show that tissue-specific deletion of mouse Cobra1 inhibits postnatal mammary gland development and that the mammary defects can be rescued by additional deletion of Brca1in a DNA repair-independent manner.
- Sreejith J. Nair
- , Xiaowen Zhang
- & Rong Li
-
Article
| Open AccessBK channel inactivation gates daytime excitability in the circadian clock
BK potassium channels have been previously shown to mediate SCN circadian firing, although the precise mechanisms are unclear. Here, using knockout and rescue approaches, the authors find that the ß2 ‘ball-and-chain’ confers BK channel inactivation during the day, promoting SCN electrical upstate.
- Joshua P. Whitt
- , Jenna R. Montgomery
- & Andrea L. Meredith
-
Article
| Open AccessItk is required for Th9 differentiation via TCR-mediated induction of IL-2 and IRF4
The Tec family tyrosine kinase, Itk, is a component of the T-cell receptor essential for optimal Th2 responses in vivo. Here the authors show in human cells and mouse models that Itk is also needed for the production of IL-9, an important contributor to allergic asthma.
- Julio Gomez-Rodriguez
- , Françoise Meylan
- & Pamela L. Schwartzberg
-
Article
| Open AccessSingle-cell differences in matrix gene expression do not predict matrix deposition
Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition.
- Allison J. Cote
- , Claire M. McLeod
- & Robert L. Mauck
-
Article
| Open AccessEAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity
EAF2 has been previously known as a transcriptional elongation factor and a proapoptotic gene lost in prostate cancer. Here the authors show that EAF2 is required for apoptosis of germinal centre B cells, and that EAF2-deficient mice develop excessive antibody responses and autoimmunity.
- Yingqian Li
- , Yoshimasa Takahashi
- & Ji-Yang Wang
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