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: 32.24). 04/2012; 149(2):322-33. DOI: 10.1016/j.cell.2012.03.012
Source: PubMed


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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    • "Recent advances in live-cell imaging and computational image analysis have generated new insights into many aspects of cell signaling. In yeast, these new tools have been combined with mathematical modeling to investigate dose alignment (Yu et al., 2008), noise regulation (Dixit et al., 2014), cell fate decisions (Doncic et al., 2011) and gradient sensing (Hao et al., 2008; Jin et al., 2011; Howell et al., 2012; Dyer et al., 2013; Kelley et al., 2015). The success of these investigations motivated us to apply a similar approach to investigate Sst2's role in regulating receptor endocytosis. "
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    • "However, when negative feedback is added to the positive feedback model, a cell becomes less susceptible to noise, causing proper polarization (right). Reprinted from Howell et al. (2012) Copyright, with permission from Elsevier. (B) BASL undergoes polarity switching during asymmetric cell division in Arabidopsis. "
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