Cell biology

  • Article
    | Open Access

    Glucocorticoids are associated with stress. Here, the authors show that high levels of glucocorticoid stress promote secretory autophagy of matrix metalloproteinase 9 via a stress responsive chaperone, increasing brain-derived neurotrophic factor processing and potentially altering adult synaptic plasticity.

    • Silvia Martinelli
    • , Elmira A. Anderzhanova
    •  & Nils C. Gassen
  • Article
    | Open Access

    Arginine methylation by PRMTs is dysregulated in cancer. Here, the authors use functional genomics screens and identify PRMT1 as a vulnerability in pancreatic ductal adenocarcinoma, and further show that PRMT1 regulates RNA metabolism and coordinates expression of genes in cell cycle progression, maintaining genomic stability and tumour growth.

    • Virginia Giuliani
    • , Meredith A. Miller
    •  & Timothy P. Heffernan
  • Article
    | Open Access

    Aβ oligomers (AβO) are thought to represent the main toxic species in Alzheimer’s disease but very high Aβ concentrations are required to study them in vitro and it remains unknown what role these off-pathway oligomers play in vivo. Here, the authors use a dimeric variant of Aβ termed dimAβ, where two Aβ40 units are linked, which facilitates to study AβO formation kinetics and they observe that Aβ off-pathway oligomer formation is strongly accelerated at endo-lysosomal pH, while amyloid fibril formation is delayed. Furthermore, the authors demonstrate that dimAβ is a disease-relevant model construct for pathogenic AβO formation by showing that dimAβ AβOs target dendritic spines and induce AD-like somatodendritic Tau missorting.

    • Marie P. Schützmann
    • , Filip Hasecke
    •  & Wolfgang Hoyer
  • Article
    | Open Access

    Here, the authors show that microglia depletion results in unstable wakefulness and altered levels of ceramide, influencing microglia in the mouse thalamic reticular nucleus (TRN). Stable wakefulness can be restored by activation of the TRN or inhibition of ceramide production in the mouse brain.

    • Hanxiao Liu
    • , Xinxing Wang
    •  & Qiaojie Xiong
  • Article
    | Open Access

    Hedgehog signaling is essential for bone formation. Here, the authors show that the transmembrane protein SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts, suggesting it may be a potential therapeutic target to enhance bone formation.

    • Jun Sun
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt
  • Article
    | Open Access

    UBE2W catalyzes the ubiquitination of protein N-termini but its substrate spectrum is largely unknown. Here, the authors discover mAbs selective for peptides derived from N-terminally ubiquitinated proteins, solve the structure of a peptide-bound mAb and apply the mAbs to map endogenous UBE2W substrates by proteomics.

    • Christopher W. Davies
    • , Simon E. Vidal
    •  & James T. Koerber
  • Article
    | Open Access

    Cytokinetic ring constriction during cell division requires actin but curiously is independent of myosin in many organisms. Here, the authors show that anillin, a protein enriched in the contractile ring, is a non-motor actin crosslinker that generates contractile force in lieu of a molecular motor.

    • Ondřej Kučera
    • , Valerie Siahaan
    •  & Zdenek Lansky
  • Article
    | Open Access

    S-acylation is the post-translational covalent attachment of fatty acids (FA) onto cysteines. Nuskova et al. find that exposure of cells to different FAs affects which FA is used to S-acylate GNAI proteins, thereby altering GNAI function and EGFR pathway activation, linking metabolism to signaling.

    • Hana Nůsková
    • , Marina V. Serebryakova
    •  & Aurelio A. Teleman
  • Article
    | Open Access

    Endoplasmic reticulum (ER)-interorganelle membrane contact sites have emerged as key regulators of organelle dynamics. Here, the authors report that the ER-resident protein SNX19 mediates ER-endolysosome membrane contacts to maintain the perinuclear distribution of endolysosomes and restrict their motility.

    • Amra Saric
    • , Spencer A. Freeman
    •  & Juan S. Bonifacino
  • Article
    | Open Access

    Patients with Cornelia de Lange Syndrome (CdLS) often have mutations in cohesin and its regulators; however, the molecular mechanism driving CdLS phenotypes is not well established. Here the authors reveal system skeletal organization genes are downregulated and show that cohesin and its loader Nipbl have altered and decreased genome-wide localization.

    • Patricia Garcia
    • , Rita Fernandez-Hernandez
    •  & Ethel Queralt
  • Article
    | Open Access

    Autosomal dominant polycystic kidney disease is characterized by the formation of cysts in the kidney. Here the authors show that cystic extracellular vesicles/exosomes play a critical role in regulating the biology and function of adjacent cells, including renal epithelial cells, fibroblasts and macrophages, and contribute to renal cyst growth.

    • Hao Ding
    • , Linda Xiaoyan Li
    •  & Xiaogang Li
  • Article
    | Open Access

    Environmental and genetic risk factors affect the distal airway epithelium in idiopatic pulmonary fibrosis (IPF) but the role of the epithelium in IPF remains unclear. Here the authors show that pathologic activation of the ERBB-YAP axis induces dynamic and structural dysfunction in the distal airway epithelium eliciting a pro-fibrotic phenotype in mesenchymal cells.

    • Ian T. Stancil
    • , Jacob E. Michalski
    •  & David A. Schwartz
  • Article
    | Open Access

    Nutrient status in the cell regulates autophagy via mTORC1 activity. Here, the authors show that the ubiquitous G protein subunit Gαq contributes to nutrient sensing by promoting formation of an mTOR-p62-Raptor complex in replete conditions, modulating autophagy.

    • Sofía Cabezudo
    • , Maria Sanz-Flores
    •  & Catalina Ribas
  • Article
    | Open Access

    BRAF-MAPK activating mutations are reported in histiocytoses—hematological neoplasms with widespread pro-inflammatory myeloid cells. Here, the authors show that an activating mutant BRAF in haematopoietic stem and progenitor cells causes an oncogene-induced senescence response leading to myeloid restricted haematopoiesis, inflammation and histiocytosis.

    • Riccardo Biavasco
    • , Emanuele Lettera
    •  & Eugenio Montini
  • Article
    | Open Access

    The serine/threonine kinase WNK1 is an inhibitor of chloride efflux. Here the authors show that this inhibition is a means of negatively regulating the activation of the NLRP3 inflammasome in macrophages, leading to reduced inflammatory responses.

    • Lindsey Mayes-Hopfinger
    • , Aura Enache
    •  & Emad S. Alnemri
  • Article
    | Open Access

    Assembly of the mitoribosome requires assistance from numerous specialized factors. Here, structures of the human 39S late assembly intermediates identify several assembly factors which keep the 16S rRNA in immature conformations, and reveal deacylated tRNA in the ribosomal E-site, suggesting a role in 39S assembly.

    • Jingdong Cheng
    • , Otto Berninghausen
    •  & Roland Beckmann
  • Article
    | Open Access

    The transmembrane protein Wntless (WLS) is essential for the secretion of Wnt proteins, which are signaling molecules of the Wnt signaling pathways. Here, the authors present the 2.2 Å cryo-EM structure of human WLS in complex with Wnt3a and discuss mechanistic implications for the palmitoleoylation of Wnt3a that is required for WLS mediated Wnt secretion.

    • Qing Zhong
    • , Yanyu Zhao
    •  & Dan Ma
  • Article
    | Open Access

    Calcium signals initiated by IP3 receptors in ER membranes regulate most cellular activities. Here, the authors show that KRas-induced actininteracting protein (KRAP) tethers a small subset of IP3 receptors to actin and licenses them to evoke cytosolic calcium signals.

    • Nagendra Babu Thillaiappan
    • , Holly A. Smith
    •  & Colin W. Taylor
  • Article
    | Open Access

    Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits YAP1 activity and may reduce proliferation-promoting transcription.

    • Daniel Feliciano
    • , Carolyn M. Ott
    •  & Jennifer Lippincott-Schwartz
  • Article
    | Open Access

    In neurons and other cells, contacts between organelles regulates function and subcellular organization, but the precise mechanisms and effects are unclear. Here the authors show that endoplasmic reticulum (ER) tubules in the soma of neurons regulate lysosome localization and function by regulating lysosomal fission, suggesting a role for ER – lysosome inter-organelle membrane contact sites in lysosomal axonal availability.

    • Nazmiye Özkan
    • , Max Koppers
    •  & Ginny G. Farías
  • Article
    | Open Access

    Reactive oxygen species (ROS) are metabolic by-products which in excess can be toxic for hematopoietic stem and progenitor cells (HSPCs). Here the authors show that toxic ROS are transferred by expanding HSPCs to the zebrafish developmental niche via connexin Cx41.8, where Ifi30 promotes their detoxification.

    • Pietro Cacialli
    • , Christopher B. Mahony
    •  & Julien Y. Bertrand
  • Article
    | Open Access

    Septins are cytoskeletal proteins that assemble into complexes and contribute to immunity by entrapping intracellular bacteria in cage-like structures. Here, Lobato-Márquez et al. reconstitute septin cages in vitro using purified recombinant complexes, and study how these recognize bacterial cells and assemble as filaments on their surface.

    • Damián Lobato-Márquez
    • , Jingwei Xu
    •  & Serge Mostowy
  • Article
    | Open Access

    Pannexin 1 (PANX1) is a membrane channel mediating release of signaling molecules to the extracellular space. PANX1 can be activated by GPCRs. Here, the authors elucidate a non-canonical channel activation pathway by α1-adrenergic receptor that involves HDAC6- mediated lysine deacetylation of PANX1.

    • Yu-Hsin Chiu
    • , Christopher B. Medina
    •  & Douglas A. Bayliss
  • Article
    | Open Access

    The cellular identity and function of the pancreatic polypeptide (Ppy)-producing γ-cells are incompletely understood. Here the authors show that these cells are heterogeneous and display adaptive plasticity to engage in insulin production following β-cell injury, but loss of the Ppy gene or γ-cells in mice does not affect weight or glycemia under basal conditions.

    • Marta Perez-Frances
    • , Léon van Gurp
    •  & Pedro L. Herrera
  • Article
    | Open Access

    Uncontrolled activation of fibroblasts contributes to tissue fibrosis and organ dysfunction. Here the authors demonstrate that the epigenetic control of autophagy is disturbed by a TGFβ-dependent downregulation of MYST1 in systemic sclerosis patients. Restoration of the epigenetic control of autophagy reduces fibroblast activation and ameliorates fibrotic tissue remodeling.

    • Ariella Zehender
    • , Yi-Nan Li
    •  & Jörg H. W. Distler
  • Article
    | Open Access

    Necroptosis, a form of cell death, occurs in acute renal injury. Here, the authors show that ferroptosis—a form of cell death dependent on iron - also occurs during acute kidney injury, and show that an inhibitor of ferroptosis can improve survival in a mouse model of acute kidney damage.

    • Wulf Tonnus
    • , Claudia Meyer
    •  & Andreas Linkermann
  • Article
    | Open Access

    Extracellular vesicles (EVs) play a role in intercellular communication, however the precise biogenesis of different populations of EVs are not clear. Here, the authors follow the intracellular trafficking of two proteins before their secretion in EVs and report the biogenesis and protein markers of EV subtypes: ectosomes budding from the plasma membrane as well as exosomes from late endosomes.

    • Mathilde Mathieu
    • , Nathalie Névo
    •  & Clotilde Théry
  • Article
    | Open Access

    Acute pancreatitis is a serious inflammatory disease, which is more severe in diabetic mice. Here the authors use mice lacking pancreatic acinar cell insulin receptors to show that this may be because insulin preserves glycolytic energy supply in acinar cell during pancreatitis, which prevents cytotoxic calcium overload and cell death.

    • Jason I. E. Bruce
    • , Rosa Sánchez-Alvarez
    •  & John A. Williams
  • Article
    | Open Access

    HAP2 is essential for gamete fusion during fertilization and is conserved among eukaryotes. Here the authors show that species-specific adhesion between Chlamydomonas plus and minus gametes initiates HAP2 to undergo a fusogenic conformational change into homotrimers via a molecular mechanism akin to that of enveloped viruses.

    • Jun Zhang
    • , Jennifer F. Pinello
    •  & William J. Snell
  • Article
    | Open Access

    Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

    • Jianli He
    • , Xun Shangguan
    •  & Jinke Cheng
  • Article
    | Open Access

    Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.

    • Stefan Prekovic
    • , Karianne Schuurman
    •  & Wilbert Zwart
  • Article
    | Open Access

    The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.

    • Colin W. Garvie
    • , Xiaoyun Wu
    •  & Heidi Greulich
  • Article
    | Open Access

    Rare earth elements are widely used in agriculture to promote plant growth. Here the authors show that aerial application of a rare earth element to the leaves triggers a graft-transmissible, RbohD- and jasmonic acid-dependent systemic signal that triggers endocytosis and mineral nutrient uptake in roots.

    • Mengzhu Cheng
    • , Lihong Wang
    •  & Zhenbiao Yang
  • Article
    | Open Access

    Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

    • Toshiko Yamazawa
    • , Takuya Kobayashi
    •  & Takashi Murayama
  • Article
    | Open Access

    Tuberous sclerosis complex (TSC) is a multiorgan disease that can lead to hyperactive mTORC1 due to deficient TSC1 or TSC2 protein function. Here, the authors find that despite high mTORC1 activity, TFEB localizes to the nucleus and drives lysosomal gene expression via a non-canonical Rag-dependent mechanism.

    • Nicola Alesi
    • , Elie W. Akl
    •  & Elizabeth P. Henske
  • Article
    | Open Access

    Accurate regulation of protein concentrations according to changes in cell volume that accompany growth and changes in biosynthetic capacity is an important component of cellular homeostasis. Here, using the model organism S. cerevisiae, the authors show how histone production is quantitatively coupled to genome content through the intrinsic properties of histone promoters.

    • Kora-Lee Claude
    • , Daniela Bureik
    •  & Kurt M. Schmoller
  • Article
    | Open Access

    Extracellular matrix protein 1 (ECM1) has been associated with cancer but the underlying molecular mechanisms are not clear. Here, the authors show that while ECM1b isoform is a tumour suppressor, the secreted isoform ECM1a promotes tumourigenesis and chemoresistance through increasing stemness and alternative mRNA splicing in ovarian cancer.

    • Huijing Yin
    • , Jingshu Wang
    •  & Gong Yang
  • Article
    | Open Access

    Cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix; the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here authors show that motile cells leave long-lived physicochemical footprints along their way, which determine their future path.

    • Joseph d’Alessandro
    • , Alex Barbier--Chebbah
    •  & Benoît Ladoux
  • Article
    | Open Access

    Non-centrosomal microtubules provide essential functions in many cells, but the mechanisms of their formation are poorly understood. Here, the authors show that during tube formation of the Drosophila salivary glands, microtubules are released from a single active centrosome via katanin, triggering recruitment of Patronin, and leading to formation of a non-centrosomal network key to the tube invagination process.

    • Ghislain Gillard
    • , Gemma Girdler
    •  & Katja Röper
  • Article
    | Open Access

    Sarcomeres, the building blocks of striated muscles, comprise ordered actomyosin arrays involved in force production. Here, the authors visualize sarcomere organization in neonatal cardiomyocytes with in situ cryo-electron tomography, revealing a reduced order of the thin filaments, their sliding and functional states enabling contraction.

    • Laura Burbaum
    • , Jonathan Schneider
    •  & Marion Jasnin