Featured
-
-
Article |
Molecular basis for control of antibiotic production by a bacterial hormone
X-ray crystallography and cryo-electron microscopy structures of the transcriptional repressor of the methylomycin gene cluster, MmfR, reveal the molecular basis for regulation of antibiotic biosynthesis by AHFCA hormones in Actinobacteria.
- Shanshan Zhou
- , Hussain Bhukya
- & Christophe Corre
-
Article |
A growth-factor-activated lysosomal K+ channel regulates Parkinson’s pathology
The identification of a lysosomal K+ channel complex—comprising AKT and the pore-forming TMEM175—provides insights into the mechanisms through which variants of the pore-forming protein affect the development of Parkinson’s disease.
- Jinhong Wie
- , Zhenjiang Liu
- & Dejian Ren
-
Article |
Inceptor counteracts insulin signalling in β-cells to control glycaemia
The insulin inhibitory receptor (inceptor) is identified as a negative regulator of insulin and IGF1 signalling that could be targeted for β-cell regeneration in treatments for diabetes.
- Ansarullah
- , Chirag Jain
- & Heiko Lickert
-
Article |
Macrophage-derived glutamine boosts satellite cells and muscle regeneration
Mouse models of muscle injuries and ageing characterized by low levels of intra-tissue glutamine are ameliorated by macrophage-specific deletion or systemic pharmacological inhibition of glutamate dehydrogenase 1, which results in constitutively high activity of glutamine synthetase.
- Min Shang
- , Federica Cappellesso
- & Massimiliano Mazzone
-
Article |
A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis
The dynamic and reversible S-palmitoylation of the transcription factor STAT3 enhances its activation and promotes the differentiation of TH17 cells.
- Mingming Zhang
- , Lixing Zhou
- & Hening Lin
-
Article |
Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.
- Kevin X. Zhang
- , Shane D’Souza
- & Richard A. Lang
-
Article |
Heterotypic cell–cell communication regulates glandular stem cell multipotency
The multipotency of basal stem cells is directly regulated by luminal cells through the secretion of TNF, and, following luminal cell ablation, the Notch, Wnt and EGFR signalling pathways reactivate basal cell multipotency.
- Alessia Centonze
- , Shuheng Lin
- & Cédric Blanpain
-
Article |
Na+ controls hypoxic signalling by the mitochondrial respiratory chain
Na+ controls the function of the mitochondrial oxidative phosphorylation system and hypoxic redox signalling through an unexpected interaction with phospholipids.
- Pablo Hernansanz-Agustín
- , Carmen Choya-Foces
- & Antonio Martínez-Ruiz
-
Article |
Glypicans shield the Wnt lipid moiety to enable signalling at a distance
Genetic studies in Drosophila combined with structural analyses show that glypicans bind palmitoylate moieties in Wnt ligands, and thus shield Wnt ligands from their aqueous environments to enable them to signal to their distant receptors.
- Ian J. McGough
- , Luca Vecchia
- & Jean-Paul Vincent
-
Article |
Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila
High levels of the sexually dimorphic hormone ecdysone, produced by active ovaries in Drosophila, promote the proliferation of stem cells in the female gut and maximize reproductive fitness, but also increase female susceptibility to age-dependent dysplasia and tumorigenesis.
- Sara Mahmoud H. Ahmed
- , Julieta A. Maldera
- & Bruce A. Edgar
-
Article |
A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome
Dysregulation of an mTORC1 substrate-specific mechanism leads to constitutive activation of TFEB, and promotes kidney cystogenesis and tumorigenesis in a mouse model of Birt–Hogg–Dubé syndrome.
- Gennaro Napolitano
- , Chiara Di Malta
- & Andrea Ballabio
-
Article |
The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis
Phosphorylation of INSIG1 and INSIG2 by PCK1 leads to a reduction in the binding of sterols, the activation of SREBP1 and SREBP2 and the downstream transcription of lipogenesis-associated genes that promote tumour growth.
- Daqian Xu
- , Zheng Wang
- & Zhimin Lu
-
Article |
FERONIA controls pectin- and nitric oxide-mediated male–female interaction
FERONIA prevents polyspermy in Arabidopsis by enabling pectin-stimulated nitric oxide accumulation at the filiform apparatus after the first pollen tube arrives, which disengages LURE1 chemoattraction to prevent late-arriving pollen tubes from entering the ovule.
- Qiaohong Duan
- , Ming-Che James Liu
- & Alice Y. Cheung
-
Article |
Mitochondrial stress is relayed to the cytosol by an OMA1–DELE1–HRI pathway
A genome-wide CRISPR interference screen shows that a signalling pathway involving OMA1, DELE1 and the eIF2α kinase HRI relays mitochondrial stress to the cytosol to trigger the integrated stress response.
- Xiaoyan Guo
- , Giovanni Aviles
- & Martin Kampmann
-
Article |
A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol
Haploid genetic screening of cells under different types of mitochondrial perturbation shows that a pathway involving OMA1, DELE1 and the eIF2α kinase HRI communicates mitochondrial stress to the cytosol to trigger the integrated stress response.
- Evelyn Fessler
- , Eva-Maria Eckl
- & Lucas T. Jae
-
Article |
Lipid availability determines fate of skeletal progenitor cells via SOX9
Lipid starvation results in skeletal progenitors favouring commitment to chondrogenic over osteogenic fate, a process mediated by FOXO transcription factors and SOX9.
- Nick van Gastel
- , Steve Stegen
- & Geert Carmeliet
-
Article |
Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis
HPCA1, a member of a previously uncharacterized subfamily of leucine-rich-repeat receptor-like kinases, is the hydrogen-peroxide sensor at the plasma membrane in Arabidopsis.
- Feihua Wu
- , Yuan Chi
- & Zhen-Ming Pei
-
Article |
TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1
RAS and TGF-β pathways regulate distinct modes of epithelial-to-mesenchymal transition via RAS-responsive element binding protein 1.
- Jie Su
- , Sophie M. Morgani
- & Joan Massagué
-
Article |
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition
Populations of KRAS(G12C)-mutant cancer cells can rapidly bypass the effects of treatment with KRAS(G12C) inhibitors because a subset of cells escapes drug-induced quiescence by producing new KRAS(G12C) that is maintained in its active, drug-insensitive state.
- Jenny Y. Xue
- , Yulei Zhao
- & Piro Lito
-
Article |
KRAS4A directly regulates hexokinase 1
KRAS4A interacts directly with hexokinase 1 in a GTP-dependent manner at the outer mitochondrial membrane, leading to kinase activation and an increase in glucose uptake and glycolysis in tumour cells.
- Caroline R. Amendola
- , James P. Mahaffey
- & Mark R. Philips
-
Article |
Plasma membrane V-ATPase controls oncogenic RAS-induced macropinocytosis
A whole-genome short interfering RNA screen identified vacuolar ATPase as a regulator of macropinocytosis induced by oncogenic RAS, a key determinant of tumour cell growth under nutrient-limiting conditions.
- Craig Ramirez
- , Andrew D. Hauser
- & Dafna Bar-Sagi
-
Article |
PGRMC2 is an intracellular haem chaperone critical for adipocyte function
Progesterone receptor membrane component 2 is required to transport haem from the mitochondria to the nucleus, where, in adipose tissue, it has roles in regulation of thermogenesis and glucose metabolism.
- Andrea Galmozzi
- , Bernard P. Kok
- & Enrique Saez
-
Article |
Structural basis of species-selective antagonist binding to the succinate receptor
High-resolution crystal structures of the rat succinate receptor SUCNR1 in an inactive confirmation, and the humanized rat SUCNR1 bound to an antagonist, provide insights into the structure of these receptors and the species selectivity of antagonist binding.
- Matthias Haffke
- , Dominique Fehlmann
- & Veli-Pekka Jaakola
-
Article |
Architecture of autoinhibited and active BRAF–MEK1–14-3-3 complexes
The autoinhibited and active states of full-length BRAF in complexes with its substrate MEK1 and the 14-3-3 protein are determined by cryo-electron microscopy.
- Eunyoung Park
- , Shaun Rawson
- & Michael J. Eck
-
Article |
Structural insights into the mechanism of human soluble guanylate cyclase
Cryo-electron microscopy structures of human soluble guanylate cyclase in inactive and activated states shed light on the activation mechanism of this enzyme by nitric oxide.
- Yunlu Kang
- , Rui Liu
- & Lei Chen
-
Letter |
DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome
The RNA helicase DDX3X has a critical role in regulating both the induction of stress granules and the activation of the NLRP3 inflammasome in cells under stress conditions.
- Parimal Samir
- , Sannula Kesavardhana
- & Thirumala-Devi Kanneganti
-
Letter |
Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation
The palmitoylation of STAT3 is mediated by fatty acids and/or the palmitoyl acyltransferase ZDHHC19, and deregulation of this palmitoylation has a role in inflammation and tumorigenesis.
- Jixiao Niu
- , Yang Sun
- & Xu Wu
-
Letter |
A calmodulin-gated calcium channel links pathogen patterns to plant immunity
The cyclic nucleotide-gated channel proteins CNGC2 and CNGC4 form a calcium channel in Arabidopsis; this channel is blocked by calmodulin in the resting state but is phosphorylated and activated upon pathogen attack, triggering an increase in cytosolic calcium levels.
- Wang Tian
- , Congcong Hou
- & Sheng Luan
-
Letter |
Smoothened stimulation by membrane sterols drives Hedgehog pathway activity
The crystal structure of active mouse SMO in complex with the SAG21k agonist and a stabilizing intracellular binding nanobody reveals the structural basis of SMO regulation by PTCH1.
- Ishan Deshpande
- , Jiahao Liang
- & Aashish Manglik
-
Letter |
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis
UDP-glucose has a tumour-suppressive role by inhibiting the association between HuR and SNAI1 mRNA, whereas UGDH-mediated metabolism of UDP-glucose leads to increased SNAI1 mRNA stability and expression, thereby promoting tumour cell migration and lung cancer metastasis.
- Xiongjun Wang
- , Ruilong Liu
- & Weiwei Yang
-
Letter |
Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric Gi
Cryo-electron microscopy structure of the human Smoothened protein bound to 24(S),25-epoxycholesterol and a heterotrimeric Gi protein provides insights into the activation of a Frizzled-class G-protein-coupled receptor and Hedgehog signal transduction.
- Xiaofeng Qi
- , Heng Liu
- & Xiaochun Li
-
Article |
Metabolic control of BRISC–SHMT2 assembly regulates immune signalling
Cryo-electron microscopy and mutation experiments demonstrate that the inactive SHMT2 dimer—and not the pyridoxal-5′-phosphate-bound tetramer—binds to BRISC, which reveals a mechanism for the regulation of deubiquitylases and inflammatory signalling.
- Miriam Walden
- , Lei Tian
- & Elton Zeqiraj
-
Letter |
SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis
The SR-B1 receptor partners with DOCK4 and RAC1 to drive the uptake and transcytosis of LDL in endothelial cells, thereby promoting atherosclerosis in mice.
- Linzhang Huang
- , Ken L. Chambliss
- & Philip W. Shaul
-
Article |
Nitrosative stress drives heart failure with preserved ejection fraction
iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.
- Gabriele G. Schiattarella
- , Francisco Altamirano
- & Joseph A. Hill
-
Letter |
Structural basis for KCTD-mediated rapid desensitization of GABAB signalling
X-ray crystallography, electron microscopy and functional experiments reveal the details of how KCTD proteins interact with GABAB receptors and desensitize G-protein-coupled inwardly rectifying potassium channels.
- Sanduo Zheng
- , Nohely Abreu
- & Andrew C. Kruse
-
Letter |
PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress
Phosphorylation of one of two adjacent serine residues in TSC2 is both required and sufficient for PKG1-mediated cardiac protection against pressure overload in mice; these serine residues provide a genetic tool for the bidirectional regulation of stress-stimulated mTORC1 activity.
- Mark J. Ranek
- , Kristen M. Kokkonen-Simon
- & David A. Kass
-
Letter |
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Single-cell analysis reveals that interactions with the extracellular matrix via integrin α5 and mechanotransducer YAP1 determine whether pancreatic progenitors develop along the duct or endocrine lineages.
- Anant Mamidi
- , Christy Prawiro
- & Henrik Semb
-
Letter |
The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ
The ARID1A-containing SWI/SNF complex operates as an inhibitor of the pro-oncogenic transcriptional coactivators YAP and TAZ; this interaction is regulated by cellular mechanotransduction.
- Lei Chang
- , Luca Azzolin
- & Stefano Piccolo
-
Letter |
Nuclear cGAS suppresses DNA repair and promotes tumorigenesis
DNA damage induces translocation of cyclic GMP–AMP synthase to the nucleus, where it suppresses homologous recombination by interfering with the formation of the PARP1–Timeless complex.
- Haipeng Liu
- , Haiping Zhang
- & Baoxue Ge
-
Letter |
GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis
During starvation, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) targets GTPase-activating proteins to inhibit multiple intracellular transport pathways, thereby promoting energy homeostasis.
- Jia-Shu Yang
- , Jia-Wei Hsu
- & Victor W. Hsu
-
Article |
Coupling of bone resorption and formation by RANKL reverse signalling
Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption.
- Yuki Ikebuchi
- , Shigeki Aoki
- & Hiroshi Suzuki
-
Letter |
Crystal structure of the Frizzled 4 receptor in a ligand-free state
The crystal structure of the Frizzled 4 receptor transmembrane domain is reported to a resolution of 2.4 Å in a ligand-free state.
- Shifan Yang
- , Yiran Wu
- & Fei Xu
-
Letter |
Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization
During sexual reproduction in Schizosaccharomyces pombe, the rapid reconstitution of a bipartite Mi–Pi transcription complex after fusion blocks re-fertilization and induces meiosis, which ensures that the genome is maintained.
- Aleksandar Vještica
- , Laura Merlini
- & Sophie G. Martin
-
Letter |
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer
Modulation of DNA 5-hydroxymethylcytosine by glucose reveals an AMPK–TET2–5hmC axis that links diabetes to cancer.
- Di Wu
- , Di Hu
- & Yujiang Geno Shi
-
Letter |
Structures of human Patched and its complex with native palmitoylated sonic hedgehog
High-resolution structures of the human plasma membrane protein patched 1 alone and in complex with the native form of the ligand sonic hedgehog are determined.
- Xiaofeng Qi
- , Philip Schmiege
- & Xiaochun Li
-
Letter |
GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells
GLI1-positive cells in the colon secrete Wnt ligands and thereby support homeostasis of intestinal stem cells.
- Bahar Degirmenci
- , Tomas Valenta
- & Konrad Basler
-
Letter |
EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle
The transition between early mitotic inhibitor 1 acting as a substrate of the APC/C and as an inhibitor of the same complex results in an irreversible switch that mediates human cell-cycle commitment.
- Steven D. Cappell
- , Kevin G. Mark
- & Tobias Meyer
-
Letter |
KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing
In response to amino acid stimulation, the ubiquitin E3 ligase CUL3–KLHL22 promotes the activation of mTORC1, which may drive tumour growth in breast cancer.
- Jie Chen
- , Yuhui Ou
- & Ying Liu
-
Article |
Catalytic activation of β-arrestin by GPCRs
Transient engagement of the G protein-coupled receptor core can act as a catalyst to activate cellular β-arrestin function after dissociation from the receptor.
- Kelsie Eichel
- , Damien Jullié
- & Mark von Zastrow
MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche