Negative feedback enhances robustness in the yeast polarity establishment circuit.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Howell, AS; Jin, M; Wu, C-F; Zyla, TR; Elston, TC; Lew, DJ

Published Date

  • April 13, 2012

Published In

Volume / Issue

  • 149 / 2

Start / End Page

  • 322 - 333

PubMed ID

  • 22500799

Pubmed Central ID

  • 22500799

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2012.03.012

Language

  • eng

Conference Location

  • United States