Negative Feedback Enhances Robustness in the Yeast Polarity Establishment Circuit

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Cell (Impact Factor: 33.12). 04/2012; 149(2):322-33. DOI: 10.1016/j.cell.2012.03.012
Source: PubMed

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.

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Available from: Chi-Fang Wu, Feb 25, 2015
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    • "It is thus possible that positive and negative feedback is operating in the HSN neuron on UNC-40 and that UNC-40 (A1056V) and UNC-53 alter these feedback mechanisms such that more stable UNC-40 clusters can be detected. Positive and negative feedback might be differently tuned in the HSN neuron to provide a cell type– specific polarity response (Novák and Tyson, 2008; Howell et al., 2012), and thus oscillations in UNC-40 cluster formation might be absent or more difficult to detect. Given that real-time imaging techniques have not yet been developed in the HSN neuron (Xu et al., 2009; Kulkarni et al., 2013), it is also possible that oscillations in UNC-40 clustering are present but have yet to be resolved. "
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