title: Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops.
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.
authors: Max-Planck-Institute of Biochemistry, Cellular Dynamics and Cell Patterning, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors: Tina
authors: T
authors: Freisinger
authors: Ben
authors: B
authors: Klünder
authors: Jared
authors: J
authors: Johnson
authors: Nikola
authors: N
authors: Müller
authors: Garwin
authors: G
authors: Pichler
authors: Gisela
authors: G
authors: Beck
authors: Michael
authors: M
authors: Costanzo
authors: Charles
authors: C
authors: Boone
authors: Richard A
authors: RA
authors: Cerione
authors: Erwin
authors: E
authors: Frey
authors: Roland
authors: R
authors: Wedlich-Söldner
mesh_terms: D000199:Actins / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D020090:Chromosome Segregation / Q000187:drug effects; D003198:Computer Simulation; D004271:DNA, Fungal / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013269:Stochastic Processes; D053778:Thiazolidines / Q000494:pharmacology; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004271:DNA, Fungal; D020730:Guanine Nucleotide Dissociation Inhibitors; D053778:Thiazolidines; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; C037068:latrunculin B
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