Cell biology articles within Nature Communications

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  • Article
    | Open Access

    The tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here the authors show that radiation induced miR-103 downregulates TREX1 in endothelial cells, decreases angiogenesis and leads to the secretion of proinflammatory mediators that reduce tumour growth.

    • RaeAnna Wilson
    • , Cristina Espinosa-Diez
    •  & Sudarshan Anand

  • Article
    | Open Access

    Renal tumour-initiating cells (T-ICs) contribute to tumour initiation and progression. Here, the authors show that lncARSR regulates TICs by blocking LATS1-induced YAP phosphorylation facilitating YAP nuclear translocation, which promotes lncARSR transcription, thus forming a feed-forward circuit to promote TIC expansion.

    • Le Qu
    • , Zhenjie Wu
    •  & Linhui Wang

  • Article
    | Open Access

    VPS15 is known as a VPS34-associated protein that functions in intracellular trafficking and autophagy. Here the authors identify a role for VPS15 in ciliopathy and ciliary phenotypes, and show that it interacts with GM130 and functions in IFT20-dependent cis-Golgi to cilium trafficking.

    • Corinne Stoetzel
    • , Séverine Bär
    •  & Hélène Dollfus

  • Article
    | Open Access

    Multivesicular bodies (MVB) are endosomal compartments that can either fuse with the plasma membrane for the secretion of exosomes, or fuse with the lysosome and be degraded along with their contents. Here, the authors show that ISGylation of the MVB protein TSG101 impairs exosome secretion and acts as a regulator of MVB fate.

    • Carolina Villarroya-Beltri
    • , Francesc Baixauli
    •  & Francisco Sánchez-Madrid

  • Article
    | Open Access

    Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.

    • Melissa F. Brereton
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Robo4 is a transmembrane protein that regulates vascular permeability. Zhang et al. now reveal the mechanism of Robo4 action and show that Robo4 and UncB are required for VEGF-mediated regulation of vascular barrier by suppressing VEGF-induced phosphorylation of its receptor Vegfr2 on Y949.

    • Feng Zhang
    • , Claudia Prahst
    •  & Anne Eichmann

  • Article
    | Open Access

    During vascular development, fibronectin (FN) is polymerized at the basolateral side of endothelial cells. Here Mana et al. propose a model where PPFIA1 drives recycling of the FN receptor, a5β1 integrin, to the cell surface and enables polar secretion and fibrillogenesis of newly synthesized FN.

    • Giulia Mana
    • , Fabiana Clapero
    •  & Donatella Valdembri

  • Article
    | Open Access

    Accumulated damage to mitochondrial DNA (mtDNA) occurs during the ageing process and neurodegenerative disease. Here, the authors show that mtDNA copy number increases in an age-dependent manner in substantia nigra of healthy individuals, but not in individuals with Parkinson disease.

    • Christian Dölle
    • , Irene Flønes
    •  & Charalampos Tzoulis

  • Article
    | Open Access

    The ubiquitin-proteasome system is thought to be the primary regulator of centrosome number. Here, Watanabe et al. show that selective autophagy also plays a role in regulating centrosome number via p62-dependent recruitment of centrosomal protein 63 to autophagosomes.

    • Yuichiro Watanabe
    • , Shinya Honda
    •  & Shigeomi Shimizu

  • Article
    | Open Access

    Atherosclerosis is caused by low-density lipoprotein (LDL) buildup in the vessel wall, a process thought to be mediated by LDL receptor alone. Here, the authors show that the endothelium can uptake LDL via ALK1, a TGFβ signalling receptor, suggesting new therapies for blocking LDL accumulation in the vessel wall.

    • Jan R. Kraehling
    • , John H. Chidlow
    •  & William C. Sessa

  • Article
    | Open Access

    Epithelial-to-mesenchymal transition is a key process in tumorigenesis but little is known about the molecular mechanism regulating such process at the translational level. Here, the authors identify a subset of mRNAs important for this process that are specifically modulated by the RNA-binding protein CELF1.

    • Arindam Chaudhury
    • , Shebna Cheema
    •  & Joel R. Neilson

  • Article
    | Open Access

    mTORC1 is known to mediate the signalling activity of amino acids. Here, the authors combine modelling with experiments and find that amino acids acutely stimulate mTORC2, IRS/PI3K and AMPK, independently of mTORC1. AMPK activation through CaMKKβ sustains autophagy under non-starvation conditions.

    • Piero Dalle Pezze
    • , Stefanie Ruf
    •  & Kathrin Thedieck

  • Article
    | Open Access

    Activation of hepatic stellate cells is a critical event in the development of fibrosis, which is driven by TGF-beta and inhibited by IFN-gamma. Here Wu et al. show that the RNA binding protein CUGBP1 is increased by TGF-beta signalling and promotes IFN-gamma mRNA degradation.

    • Xingxin Wu
    • , Xudong Wu
    •  & Qiang Xu

  • Article
    | Open Access

    Centromeres are centrochromatin domains with CENP-A and H3 nucleosomes carrying transcription-associated modifications. Here the authors target synthetic modules to the centromeres to show that transcription plus histone modifications are required for CENP-A assembly and centrochromatin maintenance.

    • Oscar Molina
    • , Giulia Vargiu
    •  & William C. Earnshaw

  • Article
    | Open Access

    Dysfunction in insulin secretion is a main driver of type 2 diabetes development. Here the authors monitor phosphoproteome modulation in cells stimulated with glucose and treated with drugs affecting glucose-mediated insulin secretion to reveal phosphorylation sites implicated in insulin secretion control and gene expression regulation.

    • Francesca Sacco
    • , Sean J. Humphrey
    •  & Matthias Mann

  • Article
    | Open Access

    Heteroplasmy, in which mutant and wild-type mitochondrial DNA (mtDNA) coexist in a cell, can result in diseases. Here the authors generate transgenic flies with heteroplasmic mtDNA in flight muscles, and show that stimulation of autophagy, or a decrease in mitofusin, promotes clearance of mutant mtDNA.

    • Nikolay P. Kandul
    • , Ting Zhang
    •  & Ming Guo

  • Article
    | Open Access

    The mechanism underlying endothelial cell responses to BMP signals is unknown. Here, the authors show that the endothelial response to pro-angiogenic BMP ligands is regulated by Notch via its effect on SMAD6, a known inhibitor of BMP intracellular signaling cascade.

    • Kevin P. Mouillesseaux
    • , David S. Wiley
    •  & Victoria L. Bautch

  • Article
    | Open Access

    Rela is a transcription factor shown to have seemingly contradictory roles in anabolism and catabolism of cartilage. Here the authors find that Rela prevents chondrocyte apoptosis and that homozygous knockout causes accelerated osteoarthritis in adults, whereas heterozygous knockout suppresses osteoarthritis by maintaining wild-type effects on apoptosis but inhibiting catabolic gene expression.

    • Hiroshi Kobayashi
    • , Song Ho Chang
    •  & Taku Saito

  • Article
    | Open Access

    β-arrestins initially contact with the phosphorylated carboxyl-terminus of GPCRs before engaging with the GPCR core. Here, the authors use a chimeric GPCR partially and fully engaged with β-arrestin1 and show that the core interaction is dispensable for receptor endocytosis and signalling.

    • Punita Kumari
    • , Ashish Srivastava
    •  & Arun K. Shukla

  • Article
    | Open Access

    Retromer is recruited to endosomes by the small GTPase Rab7 and sorting nexin 3. Here, the authors report the interaction between a GTPase-activating protein TBC1d5 and Rab7, examine the biochemical details of the interaction with retromer, and discuss the implications for receptor trafficking.

    • Da Jia
    • , Jin-San Zhang
    •  & Michael K. Rosen

  • Article
    | Open Access

    Carriers of haemoglobinopathies are protected from severe malaria, likely due to reduced surface expression of virulence factors. Here, Cyrklaff et al. show that, similar to haemoglobinopathies, a transient oxidative insult affects actin reorganization and mitigates the development of cerebral malaria in mice.

    • Marek Cyrklaff
    • , Sirikamol Srismith
    •  & Michael Lanzer

  • Article
    | Open Access

    The deposition of histone H3 variant CENP-A bound with histone H4 is a key feature designating the centromere region of a chromosome. Here the authors show acetylation on residues K5 and K12 in histone H4, mediated by the RbAp46/48-Hat1 complex, is required for deposition of CENP-A-H4 into centromeres.

    • Wei-Hao Shang
    • , Tetsuya Hori
    •  & Tatsuo Fukagawa

  • Article
    | Open Access

    The synaptonemal complex is a meiosis-specific proteinaceous structure that supports homologous chromosome pairs during meiosis. Here, the authors show that SIX6OS1 (of previously unknown function) is part of the synaptonemal complex central element and upon deletion in mice, causes defective chromosome synapsis and infertility.

    • Laura Gómez-H
    • , Natalia Felipe-Medina
    •  & Alberto M. Pendas

  • Article
    | Open Access

    Signalling pathways that mediate macrophage activation in disease are poorly understood. Here the authors show that inhibition of PARP9 and/or activation of PARP14 may attenuate macrophage-mediated vascular diseases, and also provide new insight into the development of effective therapies for other inflammatory disorders.

    • Hiroshi Iwata
    • , Claudia Goettsch
    •  & Masanori Aikawa

  • Article
    | Open Access

    Epidermal growth factor receptors have been shown to oligomerise upon binding to their cognate ligands. Here, the authors use biochemical, biophysical and cell biology techniques to analyse the structures of these oligomers, and argue that these formations are required for signalling.

    • Sarah R. Needham
    • , Selene K. Roberts
    •  & Marisa L. Martin-Fernandez

  • Article
    | Open Access

    The coupling of optogenetics with fluorescent Ca2+ sensors is confounded by sensitivity of optogenetic probes to light used to excite the sensors. Here the authors develop a Ca2+ sensor based on bioluminescence resonance energy transfer (BRET) that monitors Ca2+fluxes in darkness without excitation.

    • Jie Yang
    • , Derrick Cumberbatch
    •  & Carl Hirschie Johnson

  • Article
    | Open Access

    It is unclear what role mitochondrial function plays in maintaining intestinal epithelial cell (IEC) homeostasis. Here, the authors deplete a mitochondrial chaperone, heat shock protein 60 (HSP60) in IEC and observe a loss of stemness and cell proliferation, and suggest this is accompanied by a compensatory release of WNT-related factors.

    • Emanuel Berger
    • , Eva Rath
    •  & Dirk Haller

  • Article
    | Open Access

    Characterization of T cell antigen specificity human blood is challenging due to the low clonal frequencies. Here the authors develop a fluorescent microscopy-based method to detect antigen-specific CD8 T cell activation, and apply it to characterize the anti-CMV repertoire.

    • Nadia Anikeeva
    • , Dolores Grosso
    •  & Yuri Sykulev

  • Article
    | Open Access

    mTOR regulates cell growth via a protein complex including mTORC1 and mTORC2, but their role in skin morphogenesis is unclear. Here, the authors delete mTORC1 and mTORC2 from the epidermis and see epidermal deficiencies but both mTORCs play distinct roles in skin morphogenesis.

    • Xiaolei Ding
    • , Wilhelm Bloch
    •  & Sabine A. Eming

  • Article
    | Open Access

    Human YME1L is a membrane-anchored AAA+ protease that maintains proteostasis in the mitochondrial inner membrane and intermembrane space. Here the authors probe the substrate-binding and degradation activities of YME1L and suggest the existence of sequence-specific degradation signals in mitochondrial proteostasis.

    • Hui Shi
    • , Anthony J. Rampello
    •  & Steven E. Glynn

  • Article
    | Open Access

    Biological applications of x-ray fluorescence (XRF) imaging are currently limited to mapping naturally occurring elements in tissues. Here, the authors encapsulate toxic elements in functionalized single walled nanotubes, and use them as non-toxic XRF contrast agents for imaging specific cellular organelles.

    • Christopher J. Serpell
    • , Reida N. Rutte
    •  & Benjamin G. Davis

  • Article
    | Open Access

    Three-dimensional culture systems and organoids for mammary glands are important to understand mammary gland development. Here, the authors identify conditions (including Neuregulin 1 and R-spondin 1) that allow the culture of organoids that are responsive to hormonal stimulation for up to 2.5 months.

    • Thierry Jardé
    • , Bethan Lloyd-Lewis
    •  & Trevor C. Dale

  • Article
    | Open Access

    Interphase microtubule organization creates a structural scaffold for cargo delivery determining cell polarity and cell shape. Here the authors show that in Drosophilaepithelia the orientation of microtubules responds to cell shape, rather than the converse, and develop a simple model to mimic this behaviour.

    • Juan Manuel Gomez
    • , Lyubov Chumakova
    •  & Nicholas H. Brown

  • Article
    | Open Access

    How neurons produce energy to fuel fast axonal transport is only partially understood. Authors here report that most glycolytic enzymes are enriched in motile vesicles, and such glycolytic machinery can produce ATP autonomously to propel vesicle movement along microtubules in a cell-free assay.

    • María-Victoria Hinckelmann
    • , Amandine Virlogeux
    •  & Frédéric Saudou

  • Article
    | Open Access

    Chromosomes bind microtubules (MT) from opposite spindle poles and the generated tension stabilizes kinetochore-MT attachments. Here the authors measure kinetochore forces by engineering two force sensors and propose that kinetochore fibers exert hundreds of pNs of force to bioriented kinetochores.

    • Anna A. Ye
    • , Stuart Cane
    •  & Thomas J. Maresca

  • Article
    | Open Access

    Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.

    • Marc N. Wein
    • , Yanke Liang
    •  & Henry M. Kronenberg

  • Article
    | Open Access

    The actomyosin cytoskeleton consists of a contractile array but how it becomes organized is not clear. Here the authors reconstitute a controllable contractile system to show that force balances at boundaries determine contraction dynamics, and spatial anisotropy leads to self-organization or aligned contractile fibres.

    • Matthias Schuppler
    • , Felix C. Keber
    •  & Andreas R. Bausch

  • Article
    | Open Access

    The intestinal stroma secretes WNT ligands but the role of WNT in intestinal repair is unclear. Here, the authors show that when WNT synthesis is ablated from stromal macrophages, the intestine morphology is normal but hypersensitive to radiation injury, implicating macrophage-derived WNT in intestinal repair.

    • Subhrajit Saha
    • , Evelyn Aranda
    •  & Jeffrey W. Pollard

  • Article
    | Open Access

    TheArabidopsisCCA1 transcription factor is a core regulator of the circadian clock. Here, the authors show that the LWD1 protein, in complex with the TCP20 or TCP22 transcription factors, acts as a co-activator of CCA1 expression contributing to elevated CCA1 expression at dawn.

    • Jing-Fen Wu
    • , Huang-Lung Tsai
    •  & Shu-Hsing Wu

  • Article
    | Open Access

    Haematopoietic stem cells rely on glycolysis for their energy demands but whether this affects their fate is unknown. Here, the authors show that forcing the cells to rely on glycolysis is important for self-renewal and that this involves a reduction in mitochondrial mass.

    • Nicola Vannini
    • , Mukul Girotra
    •  & Matthias P. Lutolf

  • Article
    | Open Access

    Tiam1 is a guanine nucleotide exchange factor for the Rho-family GTPase Rac1. Here, the authors show that nuclear Tiam1 and Rac1 bind to RORγt on the IL-17 promoter, activating its transcription, and that inhibiting Tiam1/Rac1 is beneficial in a mouse model of autoimmunity.

    • Ahmed T. Kurdi
    • , Ribal Bassil
    •  & Wassim Elyaman

  • Article
    | Open Access

    The role of force in activating integrin cell adhesion receptors is not known. Here the authors develop fluorescent tension sensors for αL and β2 integrins and show that in migrating T cells force is transduced across the β2 integrin, and that this correlates with an active conformational state.

    • Pontus Nordenfelt
    • , Hunter L. Elliott
    •  & Timothy A. Springer

  • Article
    | Open Access

    Podosomes are adhesive cytoskeletal structures found in several cell types, but whether or how they are interconnected is not known. Here the authors demonstrate mesoscale connectivity of podosome clusters by imaging directional flow patterns of podosome components vinculin, talin and F-actin.

    • Marjolein B. M. Meddens
    • , Elvis Pandzic
    •  & Alessandra Cambi

  • Article
    | Open Access

    The protein Mdm10 is known to be present in the endoplasmic reticulum-mitochondria encounter structure (ERMES) and in mitochondrial sorting and assembly machinery (SAM). Here, the authors examine how this protein interacts with SAM and EMRES, showing that the SAM-mediated protein machinery is independent of ERMES.

    • Lars Ellenrieder
    • , Łukasz Opaliński
    •  & Thomas Becker

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