Cell biology articles within Nature Communications

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  • Article
    | Open Access

    Membrane fusion in cells is triggered by an increase in Ca2+ and involves SNARE complexes and calcium-sensing proteins, but the mechanism underlying the Ca2+-sensors’ role in fusion remains unclear. Here the authors show in vitro that the Ca2+-sensor Doc2b acts directly on membranes and induces a hemifusion intermediate in the presence of calcium.

    • Ineke Brouwer
    • , Asiya Giniatullina
    •  & Alexander J. Groffen

  • Article
    | Open Access

    Mapping the nanoscale height and dynamics of structures within the cell is difficult. Here the authors present a two-wavelength total internal reflection fluorescence method to perform real-time imaging with nanometre axial resolution using a conventional microscope.

    • Daniel R. Stabley
    • , Thomas Oh
    •  & Khalid Salaita

  • Article
    | Open Access

    Cancer patients often respond well to primary treatment but then develop resistance. Here, Misale et al. show that dual treatment with EGFR and MEK inhibitors block resistance in mice containing patient-derived xenografts and provide a mathematical model that describes the temporal development of resistant tumour clones.

    • Sandra Misale
    • , Ivana Bozic
    •  & Alberto Bardelli

  • Article
    | Open Access

    PI3K is activated as a result of insulin receptor (IR) signalling. Here the authors show that activation of specific class III PI3Ks in response to insulin promotes IR endocytosis and lysosomal degradation, providing negative feedback on IR signalling by reducing the time IR is activated.

    • Ivan Nemazanyy
    • , Guillaume Montagnac
    •  & Ganna Panasyuk

  • Article
    | Open Access

    Mice lacking RIIβ, a regulatory subunit of protein kinase A, are lean and resistant to diet-induced obesity. Here, the authors show that RIIβ regulates leptin sensitivity, acting as a physiological brake on leptin responsiveness and the duration of leptin signalling in the hypothalamus.

    • Linghai Yang
    •  & G. Stanley McKnight

  • Article
    | Open Access

    Hsp70 chaperones are essential for cellular proteostasis, and their function depends on allosteric communication between their nucleotide- and substrate-binding domains. Here, Kityk et al.provide a mechanical model of allostery and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis.

    • Roman Kityk
    • , Markus Vogel
    •  & Matthias P. Mayer

  • Article
    | Open Access

    The specification of positional values along the proximo-distal axis (shoulder to digits) of the vertebrate limb is an unresolved issue. By using heterochronic transplants of distal mesenchyme, the authors show that the zeugopod and autopod (elbow to digits) are progressively specified in an intrinsically timed manner.

    • Patricia Saiz-Lopez
    • , Kavitha Chinnaiya
    •  & Matthew Towers

  • Article
    | Open Access

    The processing of RNAs transcribed by RNA polymerase II requires a cap-binding complex (CBC), consisting of NCBP1 and NCBP2. Here, the authors report an alternative CBC formed by NCBP1 and a previously uncharacterized protein, NCBP3 that is critical for RNA processing under cellular stress conditions.

    • Anna Gebhardt
    • , Matthias Habjan
    •  & Andreas Pichlmair

  • Article
    | Open Access

    Telomeres in post-crisis cells are maintained by re-activated telomerase or by alternative lengthening of telomeres (ALT). Here, Seo et al. report a stable mode of ALT in worm where internal genomic regions generate a genomic reservoir ready to be incorporated into telomeres upon ALT activation.

    • Beomseok Seo
    • , Chuna Kim
    •  & Junho Lee

  • Article
    | Open Access

    The endothelial secreted protein Del-1 plays a role in limiting inflammation, and its deficiency is associated with pathology in periodontitis and multiple sclerosis. Here the authors show that the negative regulation of Del-1 by IL-17 involves targeting the transcription factor C/EBPß in a GSK-3ß- dependent manner.

    • Tomoki Maekawa
    • , Kavita Hosur
    •  & George Hajishengallis

  • Article
    | Open Access

    Leiomodins and Tropomodulins are related, but have different functions; actin filament nucleation and pointed end capping, respectively. Here, the authors use structural, biochemical and cellular approaches to show how these different activities have evolved based on a common protein fold.

    • Malgorzata Boczkowska
    • , Grzegorz Rebowski
    •  & Roberto Dominguez

  • Article
    | Open Access

    Selective biallelic expression of certain genes through genomic imprinting are known to play a role in controlling neurogenesis in the adult mammalian brain. Here the authors investigate the role of imprinting in the dosage control of Igf2 and its relevance for the function of IGF2 as a neurogenic regulator in the mouse brain.

    • S. R. Ferrón
    • , E. J. Radford
    •  & A. C. Ferguson-Smith

  • Article
    | Open Access

    Cytoplasmic dynein is a dimeric protein that steps processively along microtubules. Here Imaiet al. present cryo-electron microscopy images of stepping D. discoideumdynein, revealing diverse microtubule-bound configurations including a hinge-dependent, motors side-by-side arrangement.

    • Hiroshi Imai
    • , Tomohiro Shima
    •  & Stan A. Burgess

  • Article
    | Open Access

    In response to brain injury, microglia extend processes to isolate the lesion. Here Choi et al. show that microglia expressing a pathogenic mutation in the Parkinson’s disease-associated LRRK2 gene show reduced motility and delayed lesion isolation in vitro and in vivodue to attenuated focal adhesion kinase activity.

    • Insup Choi
    • , Beomsue Kim
    •  & Eun-Hye Joe

  • Article
    | Open Access

    The calcium-regulated gelsolin family of actin-binding proteins includes adseverin. Here, the authors report the X-ray crystal structure of the N-terminal portion of adseverin and use small-angle scattering and molecular dynamics simulations to examine the calcium-dependent function of this protein.

    • Sakesit Chumnarnsilpa
    • , Robert C. Robinson
    •  & Cedric Leyrat

  • Article
    | Open Access

    Glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by T cells, has immunostimulatory effect but the underlying mechanism is not clear. Here the authors show that GITR ligation inhibits the induction of Foxp3 expression and diverts CD4 T cells towards Th9 differentiation instead of iTreg.

    • Xiang Xiao
    • , Xiaomin Shi
    •  & Xian Chang Li

  • Article
    | Open Access

    Endocytosis typically directs proteins on a recycling route back to the plasma membrane, transport to the Golgi apparatus or delivery to the lysosome. Here Chaumet et al.describe a population of vesicles that can fuse directly with the outer nuclear membrane and deliver cargo into the nuclear envelope, where it can be translocated into the nucleoplasm.

    • Alexandre Chaumet
    • , Graham D. Wright
    •  & Frederic Bard

  • Article
    | Open Access

    The target of rapamycin complex 1 (TORC1) pathway couples nutrient availability with cell growth and division by destabilizing the cyclin-dependent kinase (CDK) inhibitor Sic1. Here the authors show that TORC1 downregulation leads to stabilization of Sic1 via phosphorylation by the MAP kinase Mpk1 and inhibition of dephosphorylation via the greatwall kinase pathway.

    • Marta Moreno-Torres
    • , Malika Jaquenoud
    •  & Claudio De Virgilio

  • Article
    | Open Access

    Direct reprogramming of cardiac fibroblasts into cardiomyocytes is an attractive strategy for heart regeneration, but it is hampered by the low efficiency of the process. Here the authors show that mouse fibroblasts can be reprogrammed with high efficiency into functional cardiomyocytes when pro-fibrotic signaling is inhibited.

    • Yuanbiao Zhao
    • , Pilar Londono
    •  & Kunhua Song

  • Article
    | Open Access

    Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.

    • San-Pin Wu
    • , Chung-Yang Kao
    •  & Sophia Y. Tsai

  • Article
    | Open Access

    Multiple extracellular matrix parameters influence cellular behaviour, but it is difficult to dissect their cooperative contributions. Here the authors describe a hydrogel system in which ligand density and substrate stiffness can be tuned orthogonally to study the contribution of combinations of these parameters simultaneously.

    • Andrew D. Rape
    • , Mikhail Zibinsky
    •  & Sanjay Kumar

  • Article
    | Open Access

    Guanine-rich oligonucleotides can fold into secondary structures known as G-quadruplexes that are proposed to have various biological roles. Here, Shivalingam et al. develop a cell-permeable, low-toxicity probe that can be used to probe interactions between G-quadruplexes and small molecules in vivo.

    • Arun Shivalingam
    • , M. Angeles Izquierdo
    •  & Ramon Vilar

  • Article
    | Open Access

    The Ndc80 complex acts as an interface between kinetochores and spindle microtubules, and is recruited to the kinetochore by several different proteins. Suzukiet al. use protein counting techniques and RNA interference to quantify the interaction stoichiometries within this intricate cellular structure.

    • Aussie Suzuki
    • , Benjamin L. Badger
    •  & Edward D. Salmon

  • Article
    | Open Access

    Small archaeal ubiquitin-like modifiers (SAMPs) have been hypothesized to be part of an ancestral version of the ubiquitin-proteasome system. Here, Anjum et al. identify a SAMP homologous to the eukaryotic ubiquitin-related modifier-1 and show that it is processed by the 20S core proteasome in S. acidocaldarius.

    • Rana S. Anjum
    • , Sian M. Bray
    •  & Nicholas P. Robinson

  • Article
    | Open Access

    Integrin-linked kinase (ILK) is known to modulate the extracellular matrix and hair follicle morphogenesis. Here, Morgner et al.show that lack of ILK causes an aberrant ratio of basement membrane laminins, activating stem cells and predisposing skin to carcinogenesis.

    • Jessica Morgner
    • , Sushmita Ghatak
    •  & Sara A. Wickström

  • Article
    | Open Access

    Cyclic guanosine monophosphate (cGMP) is a cellular second messenger involved in many processes including regulation of neuronal excitability and vascular tone. Gao, Nagpalet al., employ a fungal rhodopsin to optogenetically control cGMP levels in multiple systems including C. eleganssensory neurons.

    • Shiqiang Gao
    • , Jatin Nagpal
    •  & Alexander Gottschalk

  • Article
    | Open Access

    Synaptic plasticity is mediated by the dynamic localization of proteins at synapses, which is partly controlled via palmitoylation of synaptic proteins. Here, the authors show how neuronal activity regulates the palmitoylation reaction through the translocation of the palmitoyl-acyl transferase DHHC5.

    • G. Stefano Brigidi
    • , Brendan Santyr
    •  & Shernaz X. Bamji

  • Article
    | Open Access

    Histone post-translational modifications such as the trimethylation of histone H3 at lysine 27 (H3K27Me3), affect DNA accessibility and transcription. Here, the authors show that Jmjd3 and Utx, two H3K27Me3 demethylases, are important for regulating the expression of genes involved in terminal thymocyte differentiation.

    • Sugata Manna
    • , Jong Kyong Kim
    •  & Rémy Bosselut

  • Article |

    Prostate cancer is regulated by androgen receptor signalling; however, progressive disease can also be androgen-independent, thus hindering antiandrogen therapy. Here, interaction of the Hippo pathway protein, YAP1, with the androgen receptor is shown to confer castration-resistant prostate cancer.

    • Gamze Kuser-Abali
    • , Ahmet Alptekin
    •  & Bekir Cinar

  • Article
    | Open Access

    The regulation of the Hedgehog (Hh) pathway by the kinase DYRK1A is controversial. Here the authors uncover a novel inhibitory activity of DYRK1A that functions to destabilize the Hh downstream transcription factor GLI1 by destabilizing actin and preventing the nuclear accumulation of protective MKL1/JMJD1A complexes.

    • Philipp Schneider
    • , Juan Miguel Bayo-Fina
    •  & Matthias Lauth

  • Article
    | Open Access

    Starvation rapidly triggers autophagy by inactivating mTORC1 signalling, however mTORC1 inhibition does not fully recapitulate this rapid induction. Wong et al.identify a parallel starvation-senstive pathway regulating autophagy, mediated by protein phosphatase 2A-dependent dephosphorylation of ULK1.

    • Pui-Mun Wong
    • , Yan Feng
    •  & Xuejun Jiang

  • Article
    | Open Access

    Aerobic glycolysis and diminished oxidative phosphorylation exhibited by tumour cells enables the production of energy necessary to support malignant proliferation. Here the authors show that UCP3 promotes mitochondrial uncoupling and prevents tumorigenesis through a mitochondrially-driven pathway of AKT inhibition.

    • Sara M. Nowinski
    • , Ashley Solmonson
    •  & Edward M. Mills

  • Article
    | Open Access

    The human serum protein apolipoprotein L1 (APOL1) is taken up by trypanosomes where it triggers cell death, forming pores in endolysosomal membranes. Vanwalleghem et al.show that APOL1 triggers both lysosomal and mitochondrial membrane permeabilization, and that the latter is responsible for trypanolysis.

    • Gilles Vanwalleghem
    • , Frédéric Fontaine
    •  & Etienne Pays

  • Article
    | Open Access

    Polarized epithelial cells orient their mitotic spindles in the plane of the sheet but the role of cell adhesion molecules in this process is poorly understood. Here Tuncay et al. show that JAM-A regulates spindle orientation by creating a gradient of PtdIns(3,4,5)P3, regulating cortical actin assembly and localizing dynactin to the cell cortex.

    • Hüseyin Tuncay
    • , Benjamin F. Brinkmann
    •  & Klaus Ebnet

  • Article
    | Open Access

    The mechanism by which PTEN mutation is melanomagenic is complicated by different PTEN functions in different cellular locations. Here, the authors identify an alternative to membrane PI3K–AKT signalling, a caveolin-1-dependent PTEN pathway that induces nuclear localization and activation of β-catenin.

    • Alejandro Conde-Perez
    • , Gwendoline Gros
    •  & Lionel Larue

  • Article |

    Transcription, like DNA replication, is an error-prone process. Vermulst et al.show that transcription errors increase with age in yeast, and find that prematurely increasing the error rate overwhelms the proteotoxic stress response, allowing aggregation-prone proteins to escape protein quality control.

    • Marc Vermulst
    • , Ashley S. Denney
    •  & Dorothy A. Erie

  • Article
    | Open Access

    Nuclear lamins mediate interactions between chromatin and the nuclear envelope, however they are also found throughout the nucleoplasm. By measuring the dynamics of different genomic loci, Bronshtein et al.show that lamin A is also required for the stability of the nuclear interior.

    • I. Bronshtein
    • , E. Kepten
    •  & Y. Garini

  • Article
    | Open Access

    The orthogonal orientation between centrioles is thought to prevent their reduplication. Shukla et al.show that Polo-like kinase 1-dependent daughter centriole maturation, reflected in increasing inter-centriolar distance, allows centriole reduplication prior to loss of orthogonal orientation.

    • Anil Shukla
    • , Dong Kong
    •  & Jadranka Loncarek

  • Article
    | Open Access

    Synaptic vesicles are efficiently retrieved after transmission but the contribution they make to future signalling remains unclear. Rey et al.find that only a subset of vesicles—typically those retrieved recently in the stimulus train—remain near the active zone and exhibit privileged use.

    • Stephanie A. Rey
    • , Catherine A. Smith
    •  & Kevin Staras

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