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PMID: 22500799 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Negative feedback enhances robustness in the yeast polarity establishment circuit.

Cell ·Vol. 149 ·No. 2 ·2012-04-13 ·Pages 322-33

Howell AS, Jin M, Wu CF, Zyla TR, Elston TC, Lew DJ

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.

MeSH Terms
Cell Polarity Feedback, Physiological Guanine Nucleotide Exchange Factors/metabolism Models, Biological Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/metabolism cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/metabolism
Chemicals
Guanine Nucleotide Exchange Factors Saccharomyces cerevisiae Proteins cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Howell Audrey S
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Jin Meng
Wu Chi-Fang
Zyla Trevin R
Elston Timothy C
Lew Daniel J
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2012.03.012
Published
2012-04-13
Pages
322-33
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3680131
Subset
IM
Grants
NIGMS NIH HHS · GM62300 · United States
NIGMS NIH HHS · R01 GM079271 · United States
NIGMS NIH HHS · GM84071 · United States
NIGMS NIH HHS · R01 GM062300 · United States
NIGMS NIH HHS · GM79271 · United States
NIGMS NIH HHS · R01 GM084071 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2012.03.012 PMC Full Text View journal details
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