Featured
-
-
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
-
Article |
Dissociation of Bak α1 helix from the core and latch domains is required for apoptosis
During apoptosis, Bak undergoes major conformational changes that lead to mitochondrial permeabilization. Here, the authors characterize changes that occur within the Bak N-terminus using a series of antibodies and a novel tethering approach, demonstrating that dissociation of the α1 helix is a key early step in the unfolding of Bak.
- Amber E. Alsop
- , Stephanie C. Fennell
- & Ruth M. Kluck
-
Article |
Cytosolic targeting factor AKR2A captures chloroplast outer membrane-localized client proteins at the ribosome during translation
Post-translational import of nuclear-encoded proteins shapes the proteome of organelles. Here, Kim et al.show that AKR2A, a critical targeting factor for chloroplast outer membrane proteins, binds to client proteins co-translationally as they exit the ribosome.
- Dae Heon Kim
- , Jae-Eun Lee
- & Inhwan Hwang
-
Article |
Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling
Matriptase, a transmembrane serine protease, has been implicated in breast cancer since its discovery, but the mechanisms of this implication have not been elucidated. Here the authors show that matriptase abrogation in vivoaffects c-Met signalling and the growth of breast cancer cells.
- Gina L. Zoratti
- , Lauren M. Tanabe
- & Karin List
-
Article |
miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β
Colorectal cancer (CRC), like many solid tumours, progresses from adenomas to carcinomas in a sequence that leads to metastasis. Here the authors show that miR1269 plays a role in CRC relapse and metastasis by regulating TGF-β activity.
- Pengcheng Bu
- , Lihua Wang
- & Xiling Shen
-
Article |
Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain
Phagocytic glia can internalize protein aggregates in vitro. Here Pearce et al. show in Drosophila that glia clear mutant huntingtin (Htt) aggregates in a scavenger receptor Draper-dependent manner in vivo, and that internalized Htt aggregates induce the prion-like conversion of wild-type Htt expressed in the glial cytoplasm.
- Margaret M. P. Pearce
- , Ellen J. Spartz
- & Ron R. Kopito
-
Article
| Open AccessA role for Kalirin-7 in nociceptive sensitization via activity-dependent modulation of spinal synapses
The development of chronic inflammatory pain is linked with functional and structural modifications in nociceptive synapses. Here the authors demonstrate that Kalrinin-7 forms an essential link between synaptic receptors and cytoskeletal elements to functionally modify spinal nociceptive synapses.
- Jianning Lu
- , Ceng Luo
- & Rohini Kuner
-
Article
| Open AccessRegulation of systemic energy homeostasis by serotonin in adipose tissues
The neurotransmitter serotonin has both central and peripheral effects. Here, the authors show that adipocyte-derived serotonin regulates organismal energy homeostasis in mice by acting on adipocyte serotonin receptors on fat cells, which regulates lipolysis and thermogenesis in white and brown fat tissue.
- Chang-Myung Oh
- , Jun Namkung
- & Hail Kim
-
Article
| Open AccessDynamic imaging of the growth plate cartilage reveals multiple contributors to skeletal morphogenesis
It is largely unknown how individual cell behaviours translate into collective cell action that underlies bone morphogenesis. Here the authors perform quantitative imaging of the long bone cartilage growth plate and identify the key cellular mechanisms of cartilage morphogenesis.
- Yuwei Li
- , Vikas Trivedi
- & Scott E. Fraser
-
Article |
The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60
ATF3, a stress mediator, regulates the activities of key cancer-associated proteins by altering their interactions with DNA or other proteins. Here, the authors report that ATF3 also regulates Tip60, a protein acetyltransferase, by promoting its enzymatic activity and increasing its protein stability.
- Hongmei Cui
- , Mingxiong Guo
- & Chunhong Yan
-
Article |
The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF
The importance of the post-translational modification by acetylation in regulating protein function is not fully understood. Here, the authors show that acetylation of the transcriptional factor PLZF promotes the assembly of a repressor complex that limits the inflammatory response mediated by NF-κB.
- Anthony J. Sadler
- , Bandar A. Suliman
- & Dakang Xu
-
Article |
Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung
Alveoli are the lung’s functional units composed of two major epithelial cell types, type I and type II. Type II cells are adult lung stem cells, but this study shows that differentiated Type I cells can also self-renew and give rise to Type II cells, revealing a bidirectional relationship between lung epithelial cell types.
- Rajan Jain
- , Christina E. Barkauskas
- & Jonathan A. Epstein
-
Article
| Open AccessEphB4 forward signalling regulates lymphatic valve development
The bidirectional Eph-ephrin signalling regulates a myriad of developmental programmes. Zhang et al. show that EphB4 forward signalling is crucial for lymphatic valve development, providing new insight into this important developmental process previously thought to be regulated by ephrinB2-dependent reverse signalling.
- Gu Zhang
- , John Brady
- & Minhong Yan
-
Article
| Open AccessRegulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy
FoxO transcription factors promote muscle atrophy in response to stresses such as low nutrient availability. By generating muscle-specific FoxO triple-knockout mice, Milan et al.identify mechanisms by which the FoxO transcriptional network coordinates autophagic and proteasomal protein degradation.
- Giulia Milan
- , Vanina Romanello
- & Marco Sandri
-
Article |
APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p
ATG7 promotes cardiomyocyte autophagy but the molecular mechanism of its regulation is unknown. Here, Wang et al.identify a long non-coding RNA dubbed autophagy promoting factor (APF) that binds and inhibits miR-188-3p, which in turn acts on ATG7, to regulate cardiac autophagy.
- Kun Wang
- , Cui-Yun Liu
- & Pei-Feng Li
-
Article
| Open AccessMitochondrial function provides instructive signals for activation-induced B-cell fates
Cell fate choices are often based on amplification of noise. Here the authors show that small initial differences in mitochondrial reactive oxygen species lead to bigger changes in mitochondrial mass and membrane potential, which then determine plasma cell fate choice of activated B cells.
- Kyoung-Jin Jang
- , Hiroto Mano
- & Manabu Sugai
-
Article |
RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock
Histamine causes vascular leakage by a direct and yet mechanistically poorly defined effect on endothelium. Here, the authors show that histamine elicits endothelial RhoA/Rock signaling and that inhibition of this pathway preserves the vascular barrier, thereby identifying novel pharmacological targets for histamine-mediated diseases.
- Constantinos M. Mikelis
- , May Simaan
- & J. Silvio Gutkind
-
Article |
Borealin dimerization mediates optimal CPC checkpoint function by enhancing localization to centromeres and kinetochores
Borealin is a subunit of the chromosomal passenger complex that prevents premature mitosis before spindle assembly is complete. Bekier et al.show that Borealin mediates recruitment of this complex to both kinetochores and centromeres via distinct mechanisms, both of which depend on Borealin dimerization.
- Michael E. Bekier
- , Travis Mazur
- & William R. Taylor
-
Article |
The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling
Ras signalling activates the transcription factor c-Jun/AP-1, but the mechanism was unclear. Here, Chakraborty et al.describe a phosphorylation–ubiquitination cascade involving MSK1 and the E3 ubiquitin ligases Trim7 and RACO-1, which mediates c-Jun activation in Ras-driven lung tumorigenesis.
- Atanu Chakraborty
- , Markus E. Diefenbacher
- & Axel Behrens
-
Article |
Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation
The protein kinase Rio1 is known to promote 40S ribosome formation in the cytoplasm. Using budding yeast, the authors here show that Rio1 also acts in the nucleus, downregulates rDNA transcription by Pol I, and activates the processing of its transcripts to ensure rDNA stability and segregation.
- Maria G. Iacovella
- , Cristina Golfieri
- & Peter De Wulf
-
Article |
Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration
It remains unclear how conflicting guidance cues are reconciled during cell motility. Lin et al.show that cell repulsion normally provoked by cell–cell contact can be suppressed during attraction to a growth factor, highlighting a cell’s ability to prioritize cues by evaluating input strengths.
- Benjamin Lin
- , Taofei Yin
- & Andre Levchenko
-
Article |
A cohesin–OCT4 complex mediates Sox enhancers to prime an early embryonic lineage
Higher order chromatin structures affect gene transcription, but how they determine cell fate is unclear. Here, the authors show that OCT4 and SALL4 alter the higher-order chromatin structure and mediate cell fate switching in embryonic cells by targeting cohesin and polycomb complexes, respectively.
- Nesrine Abboud
- , Thomas Moore- Morris
- & Michel Pucéat
-
Article |
RECQ5-dependent SUMOylation of DNA topoisomerase I prevents transcription-associated genome instability
DNA topoisomerase I (TOP1) maintains DNA topology by relaxing supercoiled DNA during transcription. Here, the authors show that SUMOylation of TOP1 is necessary for its association with transcriptionally active RNA polymerase II and can reduce R-loops, preventing TOP1-induced DNA damage.
- Min Li
- , Subhash Pokharel
- & Yilun Liu
-
Article |
The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo
Planar cell polarity (PCP) is generated by the restricted localization of membrane-bound multiprotein complexes, but how they are trafficked to the correct location is unknown. Here, the authors show that the GTPase ARF1 and the AP-1 adaptor complex are major regulators of PCP protein trafficking in vivo.
- Jose Maria Carvajal-Gonzalez
- , Sophie Balmer
- & Marek Mlodzik
-
Article |
A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid gradient between membranes
The lipid transfer protein Osh4p is able to exchange sterol, made at the endoplasmic reticulum, for Golgi-synthesized PI(4)P. Here the authors provide direct evidence that Osh4p can transport sterol against its concentration gradient between membranes, powered by dissipation of a PI(4)P gradient.
- Joachim Moser von Filseck
- , Stefano Vanni
- & Guillaume Drin
-
Article |
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
-
Article
| Open AccessSymportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site
Biogenesis of the 80S ribosome involves more than 200 pre-ribosomal factors, which ensure the sequential assembly of ribosomal proteins and RNAs. Here the authors show that the nuclear transport adaptor Syo1 shields the 5S RNP-docking site on RpL11 before incorporation into the pre-60S through molecular mimicry.
- Fabiola R. Calviño
- , Satyavati Kharde
- & Irmgard Sinning
-
Article |
Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle
The balancing apparatus of the inner ear relies on the mechanosensory activity of hair cells (HC), which are poorly regenerated upon loss in adult mammals. Here, the authors show that in newborn mice HC regenerate through proliferation and transdifferentiation of activated striolar supporting cells that express Lgr5.
- Tian Wang
- , Renjie Chai
- & Alan G. Cheng
-
Article
| Open AccessSphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum et al.show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.
- Claudia Nussbaum
- , Sarah Bannenberg
- & Bodo Levkau
-
Article |
The Parkinson’s-associated protein DJ-1 regulates the 20S proteasome
Mutations in the gene encoding DJ-1 are associated with early-onset familial forms of Parkinson’s disease, and several different molecular functions have been attributed to this protein. Moscovitz et al.show that DJ-1 physically binds the 20S proteasome and inhibits its degradation activity.
- Oren Moscovitz
- , Gili Ben-Nissan
- & Michal Sharon
-
Article |
Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells
Transcriptional regulators Sox2 and YAP maintain expression of stemness genes in normal and cancerous cells. Here the authors show that, in osteosarcomas, Sox2 activates YAP by directly repressing transcription of its upstream negative regulators Nf2 and WWC1, promoting cancer cell stemness.
- Upal Basu-Roy
- , N. Sumru Bayin
- & Claudio Basilico
-
Article
| Open AccessGlycogen synthase kinase 3β ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production
GSK3β is a molecular hub implicated in regulation of cell metabolism, migration, proliferation and survival. Here the authors show that GSK3β regulates inflammatory cytokine production by promoting the assembly of a signalling platform downstream of TLR3, a sensor of viral infection.
- Ryeojin Ko
- , Jin Hee Park
- & Soo Young Lee
-
Article
| Open AccessA muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling
Skeletal muscle proteolysis can affect organismal energy homeostasis. Here, the authors provide molecular insight into this process by showing that muscle-derived alanine acts as a signal that triggers FGF21 secretion from the liver, which then regulates lipolysis and browning of white fat tissue.
- Noriaki Shimizu
- , Takako Maruyama
- & Hirotoshi Tanaka
-
Article |
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
-
Article
| Open AccessGlobal analysis of fungal morphology exposes mechanisms of host cell escape
Several pathogenic fungi such as Candida albicans undergo transitions between single-celled forms and multicellular filaments. Here the authors perform a genome-scale analysis of C. albicansand show that, contrary to common belief, filamentation is not required for escape from host immune cells.
- Teresa R. O’Meara
- , Amanda O. Veri
- & Leah E. Cowen
-
Article |
Immune complexes regulate bone metabolism through FcRγ signalling
Bone and the immune system are functionally intertwined. This study shows that osteoclastogenesis is modulated by the intensity of Fcγ receptor signalling, which is shaped by the balance between the positive and negative Fcγ receptors expressed on osteoclasts and the availability of their ligands, immune complexes.
- Takako Negishi-Koga
- , Hans-Jürgen Gober
- & Hiroshi Takayanagi
-
Article
| Open AccessCmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control
Defects in the DNA replication checkpoint can lead to genomic instability and cancer. Here the authors show that Cmr1/WDR76 participates in the DNA replication stress response and—along with several other components—defines a new cellular compartment that forms during cellular stress.
- Irene Gallina
- , Camilla Colding
- & Michael Lisby
-
Article |
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
-
Article |
Skp2–MacroH2A1–CDK8 axis orchestrates G2/M transition and tumorigenesis
Skp2 forms part of the SCF complex—an E3 ubiquitin ligase. Here the authors identify macroH2A1 as a novel target of Skp2 and propose an axis of regulation involving Skp2-macroH2A1-CDK8-p27 in cancer.
- Dazhi Xu
- , Chien-Feng Li
- & Hui-Kuan Lin
-
Article |
The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain
The epithalamus exhibits left-right asymmetries with different magnitudes among vertebrates. Here, the authors show that the catshark and two lampreys have conserved molecular asymmetries between the left and right developing epithalamus which are controlled by nodal signalling.
- Ronan Lagadec
- , Laurent Laguerre
- & Agnès Boutet
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