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Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops

Tina Freisinger, Ben Klünder, Jared Johnson, Nikola Müller, Garwin Pichler, Gisela Beck, Michael Costanzo, Charles Boone, Richard A. Cerione, Erwin Frey () and Roland Wedlich-Söldner ()
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Tina Freisinger: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning
Ben Klünder: Arnold Sommerfeld Center for Theoretical Physics, and Centre for Nanoscience
Jared Johnson: Baker Laboratory, Cornell University
Nikola Müller: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning
Garwin Pichler: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning
Gisela Beck: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning
Michael Costanzo: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Charles Boone: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Richard A. Cerione: Baker Laboratory, Cornell University
Erwin Frey: Arnold Sommerfeld Center for Theoretical Physics, and Centre for Nanoscience
Roland Wedlich-Söldner: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Establishment of cell polarity—or symmetry breaking—relies on local accumulation of polarity regulators. Although simple positive feedback is sufficient to drive symmetry breaking, it is highly sensitive to stochastic fluctuations typical for living cells. Here, by integrating mathematical modelling with quantitative experimental validations, we show that in the yeast Saccharomyces cerevisiae a combination of actin- and guanine nucleotide dissociation inhibitor-dependent recycling of the central polarity regulator Cdc42 is needed to establish robust cell polarity at a single site during yeast budding. The guanine nucleotide dissociation inhibitor pathway consistently generates a single-polarization site, but requires Cdc42 to cycle rapidly between its active and inactive form, and is therefore sensitive to perturbations of the GTPase cycle. Conversely, actin-mediated recycling of Cdc42 induces robust symmetry breaking but cannot restrict polarization to a single site. Our results demonstrate how cells optimize symmetry breaking through coupling between multiple feedback loops.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2795

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DOI: 10.1038/ncomms2795

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