title: Negative feedback enhances robustness in the yeast polarity establishment circuit.
abstract: Many cells undergo symmetry-breaking polarization toward a randomly oriented "front" in the absence of spatial cues. In budding yeast, such polarization involves a positive feedback loop that enables amplification of stochastically arising clusters of polarity factors. Previous mathematical modeling suggested that, if more than one cluster were amplified, the clusters would compete for limiting resources and the largest would "win," explaining why yeast cells always make one and only one bud. Here, using imaging with improved spatiotemporal resolution, we show the transient coexistence of multiple clusters during polarity establishment, as predicted by the model. Unexpectedly, we also find that initial polarity factor clustering is oscillatory, revealing the presence of a negative feedback loop that disperses the factors. Mathematical modeling predicts that negative feedback would confer robustness to the polarity circuit and make the kinetics of competition between polarity factor clusters relatively insensitive to polarity factor concentration. These predictions are confirmed experimentally.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Audrey S
authors.initials: AS
authors.lastname: Howell
authors.forename: Meng
authors.initials: M
authors.lastname: Jin
authors.forename: Chi-Fang
authors.initials: CF
authors.lastname: Wu
authors.forename: Trevin R
authors.initials: TR
authors.lastname: Zyla
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Elston
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lew
mesh_terms: D016764:Cell Polarity; D025461:Feedback, Physiological; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae