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End date: 2019 × Start date: 2019 × DDC: 570 × Type: Text × Publisher: London : Nature Publishing Group ×

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Now showing 1 - 4 of 4
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    Size control in mammalian cells involves modulation of both growth rate and cell cycle duration
    (London : Nature Publishing Group, 2018) Cadar, Clotilde; Monnier, Sylvain; Grilli, Jacopo; Sáez, Pablo J.; Srivastava, Nishit; Attia, Rafaele; Terriac, Emmanuel; Baum, Buzz; Cosentino-Lagomarsino, Marco; Piel, Matthieu
    Despite decades of research, how mammalian cell size is controlled remains unclear because of the difficulty of directly measuring growth at the single-cell level. Here we report direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells. We find that, in a majority of cell types, the volume added across the cell cycle shows little or no correlation to cell birth size, a homeostatic behavior called “adder”. This behavior involves modulation of G1 or S-G2 duration and modulation of growth rate. The precise combination of these mechanisms depends on the cell type and the growth condition. We have developed a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells. This reveals that a near-adder behavior is the most common type of size control and highlights the importance of growth rate modulation to size control in mammalian cells.
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    Dissection of iron signaling and iron accumulation by overexpression of subgroup Ib bHLH039 protein
    (London : Nature Publishing Group, 2017) Naranjo-Arcos, Maria Augusta; Maurer, Felix; Meiser, Johannes; Pateyron, Stephanie; Fink-Straube, Claudia; Bauer, Petra
    Iron is an essential growth determinant for plants, and plants acquire this micronutrient in amounts they need in their environment. Plants can increase iron uptake in response to a regulatory transcription factor cascade. Arabidopsis thaliana serves as model plant to identify and characterize iron regulation genes. Here, we show that overexpression of subgroup Ib bHLH transcription factor bHLH039 (39Ox) caused constitutive iron acquisition responses, which resulted in enhanced iron contents in leaves and seeds. Transcriptome analysis demonstrated that 39Ox plants displayed simultaneously gene expression patterns characteristic of iron deficiency and iron stress signaling. Thereby, we could dissect iron deficiency response regulation. The transcription factor FIT, which is required to regulate iron uptake, was essential for the 39Ox phenotype. We provide evidence that subgroup Ib transcription factors are involved in FIT transcriptional regulation. Our findings pose interesting questions to the feedback control of iron homeostasis.
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    The bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles
    (London : Nature Publishing Group, 2013) Matkovic, Tanja; Siebert, Matthias; Knoche, Elena; Depner, Harald; Mertel, Sara; Owald, David; Schmidt, Manuela; Thomas, Ulrich; Sickmann, Albert; Kamin, Dirk; Hell, Stefan W.; Bürger, Jörg; Hollmann, Christina; Mielke, Thorsten; Wichmann, Carolin; Sigrist, Stephan J.
    Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components intersect with SV release remains insufficiently understood. We showed previously that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP) eliminates the cytomatrix (T bar) and declusters Ca2+ channels. In this paper, we explored additional functions of the cytomatrix, starting with the biochemical identification of two BRP isoforms. Both isoforms alternated in a circular array and were important for proper T-bar formation. Basal transmission was decreased in isoform-specific mutants, which we attributed to a reduction in the size of the readily releasable pool (RRP) of SVs. We also found a corresponding reduction in the number of SVs docked close to the remaining cytomatrix. We propose that the macromolecular architecture created by the alternating pattern of the BRP isoforms determines the number of Ca2+ channel-coupled SV release slots available per AZ and thereby sets the size of the RRP.
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    Lipid droplets as a novel cargo of tunnelling nanotubes in endothelial cells
    (London : Nature Publishing Group, 2015) Astanina, Ksenia; Koch, Marcus; Jüngst, Christian; Zumbusch, Andreas; Kiemer, Alexandra K.
    Intercellular communication is a fundamental process in the development and functioning of multicellular organisms. Recently, an essentially new type of intercellular communication, based on thin membrane channels between cells, has been reported. These structures, termed intercellular or tunnelling nanotubes (TNTs), permit the direct exchange of various components or signals (e.g., ions, proteins, or organelles) between non-adjacent cells at distances over 100 μm. Our studies revealed the presence of tunnelling nanotubes in microvascular endothelial cells (HMEC-1). The TNTs were studied with live cell imaging, environmental scanning electron microscopy (ESEM), and coherent anti-Stokes Raman scattering spectroscopy (CARS). Tunneling nanotubes showed marked persistence: the TNTs could connect cells over long distances (up to 150 μm) for several hours. Several cellular organelles were present in TNTs, such as lysosomes and mitochondria. Moreover, we could identify lipid droplets as a novel type of cargo in the TNTs. Under angiogenic conditions (VEGF treatment) the number of lipid droplets increased significantly. Arachidonic acid application not only increased the number of lipid droplets but also tripled the extent of TNT formation. Taken together, our results provide the first demonstration of lipid droplets as a cargo of TNTs and thereby open a new field in intercellular communication research.