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      Inflating bacterial cells by increased protein synthesis

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          Abstract

          Understanding how the homeostasis of cellular size and composition is accomplished by different organisms is an outstanding challenge in biology. For exponentially growing Escherichia coli cells, it is long known that the size of cells exhibits a strong positive relation with their growth rates in different nutrient conditions. Here, we characterized cell sizes in a set of orthogonal growth limitations. We report that cell size and mass exhibit positive or negative dependences with growth rate depending on the growth limitation applied. In particular, synthesizing large amounts of “useless” proteins led to an inversion of the canonical, positive relation, with slow growing cells enlarged 7- to 8-fold compared to cells growing at similar rates under nutrient limitation. Strikingly, this increase in cell size was accompanied by a 3- to 4-fold increase in cellular DNA content at slow growth, reaching up to an amount equivalent to ∼8 chromosomes per cell. Despite drastic changes in cell mass and macromolecular composition, cellular dry mass density remained constant. Our findings reveal an important role of protein synthesis in cell division control.

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          Coordination of bacterial proteome with metabolism by cyclic AMP signalling.

          The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
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            Nuclear size control in fission yeast

            Along-standing biological question is how a eukaryotic cell controls the size of its nucleus. We report here that in fission yeast, nuclear size is proportional to cell size over a 35-fold range, and use mutants to show that a 16-fold change in nuclear DNA content does not influence the relative size of the nucleus. Multi-nucleated cells with unevenly distributed nuclei reveal that nuclei surrounded by a greater volume of cytoplasm grow more rapidly. During interphase of the cell cycle nuclear growth is proportional to cell growth, and during mitosis there is a rapid expansion of the nuclear envelope. When the nuclear/cell (N/C) volume ratio is increased by centrifugation or genetic manipulation, nuclear growth is arrested while the cell continues to grow; in contrast, low N/C ratios are rapidly corrected by nuclear growth. We propose that there is a general cellular control linking nuclear growth to cell size.
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              Cell size control in yeast.

              Cell size is an important adaptive trait that influences nearly all aspects of cellular physiology. Despite extensive characterization of the cell-cycle regulatory network, the molecular mechanisms coupling cell growth to division, and thereby controlling cell size, have remained elusive. Recent work in yeast has reinvigorated the size control field and suggested provocative mechanisms for the distinct functions of setting and sensing cell size. Further examination of size-sensing models based on spatial gradients and molecular titration, coupled with elucidation of the pathways responsible for nutrient-modulated target size, may reveal the fundamental principles of eukaryotic cell size control. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Mol Syst Biol
                Mol. Syst. Biol
                msb
                Molecular Systems Biology
                John Wiley & Sons, Ltd (Chichester, UK )
                1744-4292
                1744-4292
                October 2015
                30 October 2015
                : 11
                : 10
                : 836
                Affiliations
                [1 ]Institute of Molecular Systems Biology, ETH Zürich Zürich, Switzerland
                [2 ]Department of Physics, University of California at San Diego La Jolla, CA, USA
                [3 ]State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University Beijing, China
                [4 ]Institute for Theoretical Studies, ETH Zürich Zürich, Switzerland
                Author notes
                *Corresponding author. Tel: +41 44 633 40 52; E-mail: basan@ 123456imsb.biol.ethz.ch
                **Corresponding author. Tel: +1 858 534 7263; E-mail: hwa@ 123456ucsd.edu
                [†]

                These authors contributed equally to this work

                Subject Categories Metabolism; Protein Biosynthesis & Quality Control; Quantitative Biology & Dynamical Systems

                Article
                10.15252/msb.20156178
                4631207
                26519362
                075715ce-b7c2-4cc1-ab0d-1d27375f3680
                © 2015 The Authors. Published under the terms of the CC BY 4.0 license

                This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 March 2015
                : 27 September 2015
                : 30 September 2015
                Categories
                Reports

                Quantitative & Systems biology
                cell size,cell division,cellular dna,cell volume,growth rate
                Quantitative & Systems biology
                cell size, cell division, cellular dna, cell volume, growth rate

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