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

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons77971

Freisinger,  Tina
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78426

Müller,  Nikola
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78509

Pichler,  Garwin
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77727

Beck,  Gisela
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78862

Wedlich-Söldner,  Roland
Wedlich-Söldner, Roland / Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Freisinger, T., Kluender, B., Johnson, J., Müller, N., Pichler, G., Beck, G., et al. (2013). Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops. NATURE COMMUNICATIONS, 4: 1807. doi:10.1038/ncomms2795.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-4641-9
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.